TW200932735A - Benzo[f]chromene and pyrano[3,2-f]chromene derivatives - Google Patents

Abstract

The present invention relates to benzo[f]chromene and pyrano[3, 2-f] chromene derivatives of the formula I in which L1, L2, R1, R2, A1, A2, Z1, Z2, m and n are as defined in Claim 1, to the preparation thereof, to the use thereof as components in liquid-crystalline media, and to electro-optical display elements which contain the liquid-crystalline media according to the invention.

Description

200932735 IX. Description of the Invention: [Technical Field] The present invention relates to benzo[f]chromene and piperaco[3,2_f]chromene derivatives, a process for the preparation thereof, and a liquid crystal medium comprising the same And an electro-optical display element containing the liquid crystal medium. In particular, the present invention relates to benzo[f]chromene and piperaco[3,2_f]chromene derivatives having a negative dielectric anisotropy. [Prior Art] ® Since the discovery of the first commercially available liquid crystal compound about 30 years ago, liquid crystals have been widely used. Known fields of application of conventional mixtures are, in particular, displays for watches and pocket computers, as well as large display panels such as those used in train stations, airports and sports fields. Other application areas are displays, navigation systems and video applications for portable computers and desktop computers. Especially for the last mentioned application, there is a high demand for response time and image contrast. The spatial arrangement of molecules in a liquid crystal has the effect of making its many properties direction dependent. Of particular importance for use in liquid crystal displays are optical, optical, and elastic anisotropy. The apparent molecules are oriented perpendicularly or parallel to the two plates of the capacitor, and the capacitors have different electrical 'valleys. The dielectric constant ε of the liquid crystal medium has a non-identical value in both directions. A substance having a dielectric constant greater than the dielectric constant of its parallel orientation when the longitudinal axis of the molecule is oriented perpendicular to the capacitor plate is referred to as positive dielectric. In other words, if the dielectric constant 8 平行 parallel to the longitudinal axis of the molecule is greater than the dielectric constant ε 丄 ' perpendicular to the longitudinal axis of the molecule, the dielectric anisotropy Δ ε = ε | | - ε_ι_ is greater than zero. Most of the liquid crystals used in conventional displays fall into this category. 135213.doc 200932735 The polarizability of the molecule and the permanent dipole moment act on the dielectric anisotropy. When a voltage is applied to the display, the molecular longitudinal axis itself is oriented in such a way that the larger dielectric constant becomes known to be effective. The strength of the interaction with the electric field depends on the difference between the two constants. In the case of a small difference, a switching voltage higher than a case where the difference is large is required. The introduction of a suitable polar group such as a nitrile group or fluorine into the liquid crystal molecules makes it possible to achieve a wide range of operating voltages. In the case of liquid crystal molecules used in conventional liquid crystal displays, the dipole moment oriented along the longitudinal axis of the molecule is greater than the dipole moment oriented perpendicular to the longitudinal axis of the molecule. In the most common ("twisted nematic," unit, a liquid crystal layer having a thickness of only about 5 μm to 1 μm is disposed between two plane-parallel glass plates, each of which has been gas-filled. A transparent conductive layer of tin oxide or indium tin oxide (yttrium) is deposited as an electrode. An equally transparent alignment layer, typically composed of a plastic (e.g., polyimide), is positioned between the films and the liquid crystal layer. The alignment layer serves to direct the longitudinal axes of adjacent liquid crystal molecules in a preferential direction by surface forces such that they are uniformly spread in the same direction, plane or at the same small inclination angle inside the surface of the display in a voltage-free state. Two layers of polarizing film capable of allowing only linearly polarized light to enter and escape are applied to the outside of the display in a specific configuration. An extremely high performance display has been produced by means of a liquid crystal oriented with a larger dipole moment parallel to the longitudinal axis of the molecule. In most cases, a mixture of 5 to 20 components is used to achieve a sufficiently wide mesophase temperature range and short response time and low threshold voltage. However, when used in, for example, a laptop, the strong viewing angle dependence of the liquid crystal display will still cause problems. The best image quality is achieved if the surface of the display is perpendicular to the viewer's viewing direction. If the display is tilted relative to the viewing direction, in some cases the imaging quality is 135213.doc 200932735. For greater comfort, attempts are being made to maximize the angle at which the display can be tilted from the viewer's viewing direction without significantly degrading the imaging quality. It has recently been attempted to improve the viewing angle dependence by using a liquid crystal compound having a dipole moment perpendicular to the longitudinal axis of the molecule greater than the dipole moment parallel to the longitudinal axis of the molecule. In this case, the dielectric anisotropy Δ ε is a negative value. In the absence of an electric field, the molecules are oriented with their longitudinal axes perpendicular to the glass surface of the display. The application of an electric field causes the molecules themselves to be oriented substantially parallel to the surface of the glass. In this way, it is possible to achieve an improvement in viewing angle dependence. This type of display is called a VA-TFT ("Vertical Alignment") display. The development of the field of liquid crystal materials is still far from being completed. In order to improve the properties of liquid crystal display elements, we are constantly trying to develop new ones that can optimize these displays. The benzochromene derivative having the following structure is disclosed in the document DE 10 2004 004 228 A1:

These tricyclic compounds differ from the present invention in the position of the heteroatoms in the ring, the substitution of the ring, and the degree of saturation of the ring. Other benzochromene derivatives which are partially unsaturated and optionally have a plurality of heteroatoms are additionally disclosed in the document WO 2007/079840 A2. SUMMARY OF THE INVENTION It is an object of the present invention to provide compounds having advantageous properties for use in liquid crystal media. In particular, these compounds should have a negative dielectric anisotropy, 135213.doc 200932735 This property makes them particularly suitable for use in liquid crystal media for VA displays. Regardless of the dielectric anisotropy of the display type, such as helium, a compound having a combination of advantageous application parameters is required. Among these parameters to be simultaneously optimized, particular mention should be made of high-definition spots, low rotational viscosities, optical anisotropy in the range of use, and mixtures for achieving the desired liquid crystal phase in the S-temperature range. nature. This object is achieved according to the invention from a compound of the general formula T

m and η are each independently 0, 1, 2 or 3, preferably 〇, ι or 2, wherein m+n$4; L] and L2 each independently represent Η, halogen, CN, CF3, CHF2, CH2F or CH3, preferably Η, F, Cl, CN or CF3; A and A each independently represent (a) 1,4 -extension base 'where =CH- may be replaced once or twice by =N- And which may be unsubstituted or independently of each other via -CN, -F, -a, -Br, -I, unsubstituted or mono- or polysubstituted by fluorine and/or gas, Ci_C6 alkyl or unsubstituted or Mono- or poly-substituted by fluorine and / or gas 135213.doc 200932735 ❿ Z1 and z2 Ci-C6 hospital mono-substituted to tetra-substituted, (b) 1,4-cyclohexylene, 〗 4 Alkenyl or anthracene, 4-cyclohexylene-alkenyl' wherein -ch2- may be substituted one or two times independently of each other via _〇_ or -S- in a manner in which the heteroatoms are not directly bonded, and Substituted or via hydrazine and/or _C1 monosubstituted or polysubstituted, or (c) bicyclo[1.1.1]penta-i,3_diyl, bicyclo[2 2 2]octyl-, di- or snail [3.3 Geng-2,6_diyl; each independently represents a single bond, _CF2o_,_0cF2--CH2CH2-'-CF2 CF2- '-CF2CH2- ' -CH2CF2- , _(C0)0-, -0(C0)-, -CH20-, -0CH2-, -CF=CH-, -CH=CF-, -CF=CF- , -CH=CH-, -〇C- or a combination of two of these groups, wherein the ruthenium atoms are not directly bonded; R1 and R2 independently of each other represent hydrogen, unsubstituted, monosubstituted by _CN Or an alkyl, alkoxy, alkenyl or alkynyl group having 1 to 15 or 2 to 15 C atoms, respectively, mono- or poly-substituted with -F, -C1 and/or -Br, wherein One or more CH 2 groups in the group may each independently pass through _〇_, _8_, _3〇2-, -C0-, -(co)o-, -o(co)- or -o(co O- is replaced by a heteroatom that is not directly bonded, or represents -F, -c-Br, -CN, -SCN, or -SF5; and ring B represents 135213.doc • 10-200932735

Wherein: A1 and A2 or Z1 and Z2 may have the same or different meanings if m or η is greater than 1, wherein ζ R1 and R2 are different when they represent Η, and wherein = 135213.doc 200932735 is in RLH and m=〇 or In the case where R2=H and η=〇, then

The cyclic oxime represents a compound of the formula "^, which has a predominantly negative value & and is therefore particularly suitable for use in a VA-TFT display. The compound of the invention preferably has a redness of less than _2 and is particularly preferably less than - βΔε, which exhibits excellent compatibility with common materials used in liquid crystal mixtures of displays. Furthermore, the compounds of the formula I according to the invention have optical anisotropy values which are particularly suitable for use in displays. The compounds of the invention preferably have greater than 0.05. And an An of less than 0.40. Φ Other physical, physicochemical or electro-optical parameters of the present invention are also advantageous for use as a compound in a liquid crystal medium. The compounds or the linear medium containing the compounds尤# has a sufficient nematic phase width and good low temperature and long-term stability and a sufficiently high clear point. The rotational viscosity of these compounds is advantageously low, especially for m+n=〇. In the substituents L1 and L2 Further, H, and especially F. Further, one or both of the groups Li and L2 preferably represent a or especially fluorine. L1 preferably represents fluorine. Li and L2 particularly preferably represent F. In the group R2 table In the case of a fluorine atom or a fluorinated alkyl group, especially if the claws simultaneously represent 0, the formula I also encompasses compounds which may have a positive total dielectric anisotropy. These compounds are thus suitable for applications such as TNTF or Ips (" A positive dielectric liquid crystal mixture used in a planar switching ") type of display. The requirements for other physical parameters, such as viscosity, are substantially the same for most applications. These 135213.doc 200932735 compounds are therefore equally suitable for such purposes. Because it has favorable parameters (all = rotational viscosity, Δη, etc.) and it is suitable for the preparation of liquid crystal mixtures. Α and Α are preferably and independently of each other, as appropriate, 4-phenylene, fluorene a substituted 1,4-cyclohexylene group (wherein _CH2_ may be substituted by one-man or two times), or an optionally substituted i,4-cyclohexylene group. If η or m If it is 2, then ring V and a2 may have the same or different meanings. A1 and A2 are particularly preferably independent of each other:

❹

- Cyclohexyl group and/or optionally substituted by fluorine. A1 and A2 are particularly preferably 1,4 1,4-phenylene groups. In one embodiment of the invention, m+n is equal to Bu A1, A2 is independent of each other 135213.doc •13· 200932735

H.-o

F

Or ❹

Z and Z are preferably independently of each other a single bond, _CH2〇, _〇CH2, -cf2o-, -OCF2-, -CF2CF2-, _CH=CH_, _CF=CH_, CH=CF_ or -CF=CF-, Particularly preferably, they are independently a single bond, _CF2〇, _〇cF2_-CH20-, -OCH2-, -CF2CF2-, -CH=CH-, -CF=CH-, -CH=CF- or -CF= CF-. Particularly preferably, Z? and Z2 are independently a single bond, -cf2o-, -ocf2-, _Ch2?, _OCH2lcf, especially a single bond. The parameters m and η preferably have a value of 〇, 1, 2 or 3 in the sum of m + n, especially a value of 〇, 1 or 2. For m+n = 〇, it is better. At least one of the groups represents F, and particularly preferably both groups represent F. Further, for m+n=〇, R1 and R2 preferably do not represent hydrogen. And R2 are preferably each independently represented independently of (1) or 2 to 7 carbon atoms, alkoxy or county, wherein each of the groups is not thinly substituted or substituted with (tetra) monosubstituted hydrazine; Hydrogen is especially preferred as the alkyl, alkoxy or alkenyl group described. HR2 in the formula 1 is particularly preferably each independently an alkyl group, an alkoxy group or an alkenyl group having 135213.doc -14·200932735 or 2 to 7 C atoms, respectively, wherein each of the groups is preferably Unsubstituted or monosubstituted or substituted by halogen. In the case of m = 0, R1 preferably represents an alkyl group or an alkoxy group, an anthracene or an F group, and particularly preferably an alkyl group having 1 to 6 C atoms.

If R1 and R2 in the formula I are each independently represented by an alkyl group having 1 to 15 C atoms and/or an alkoxy group (alkyloxy group), the groups are straight-chain or branched. Each of these groups is preferably linear, having 1, 2, 3, 4, 5, 6 or 7 C atoms and is therefore preferably fluorenyl, ethyl, propyl, butyl, pentyl, hexyl, Heptyl, decyloxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy or heptyloxy. R1 and R2 in the formula I may each independently be an oxaalkyl group, and at least one non-terminal CH2 group has been substituted with an alkyl group, preferably a straight oxime-oxapropyl group (= Methoxyfluorenyl), 2_oxabutyl (=ethoxymethyl) or 3 oxabutylmethoxyethyl), 2 oxapentyl, 3 • oxapentyl or erythro Base, 2 oxahexyl, 3 oxahexyl, 4 oxahexyl or 5-oxahydanyl, or 2-oxaheptyl, 3 oxaheptyl, 4 oxaheptyl, % oxygen Brocade = or 6-oxaheptyl. In a corresponding way, the style! In the middle, he went to Qianji or Weiji, that is, an alkyl group called the base circle (4) or -s〇2. Further, R 丨 and R 2 in the formula 1 may further have a white i atom (4). Further, each of them independently has 2 to 15 [alkenyl groups] which are straight or branched and have an ancient bond. It is preferably straight-chain and has 2 to 2 fluorenes having at least one C-C double-B, A, = atom. Therefore, it is preferably a butyl-Li group or a propyl group, a butyl group, a benzyl group, an alkenyl 'pent-2-enyl group, a pentyl 3 alkenyl group or a pentane 135213.doc 200932735 group, a hex-1-enyl group, Hex-2-enyl, hex-3-enyl, hex-4-enyl or hexenyl, or hept-1-enyl, hept-2-enyl, hept-3-enyl, hept-4 Alkenyl, hept-5-alkenyl or heptenyl. If the two c atoms of the c_c double bond are substituted, the dilute group may be in the form of the E and/or Z isomer (trans/cis). In general, the individual E isomers are preferred. In the same manner as the alkyl group, at least one CH2 group in the alkenyl group may also be replaced by oxygen, sulfur or -S〇2-"in the case of _〇_ substitution, thus the presence of a dilute oxy group (with terminal oxygen) Or oxaalkenyl (having non-terminal oxygen). R1 and R2 in the formula I may also be, independently of each other, a fast radical having 2 to ^ atoms, which is a straight or branched bond and has at least one c_c bond. R1 and R2 in the formula I may each independently be an alkyl group having 1 to ^ atoms, wherein one CHZ group has been replaced and one ch2 group has been CO-substituted, wherein the substitutions are preferably adjacent. Thus, this contains a fluorenyl-co-o. or an oxycarbonyl s_〇_c〇_. This group is preferably straight-chain and has 2 to 6 C atoms. The following groups are preferred herein: ethoxylated, propyloxy, butyloxy, pentyloxy, hexyloxy, ethoxymethyl, propyloxy fluorenyl , butyl fluorenyl fluorenyl, pentyloxy fluorenyl, 2-ethyloxyethyl, 2-propenyloxyethyl, 2-butyloxyethyl, 3-ethoxypropyl , 3-propoxypropyl, 4-methoxyoxybutyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, pentyloxycarbonyl, decyloxycarbonylmethyl , ethoxycarbonylmethyl, propoxycarbonylmethyl, butoxycarbonylmethyl, 2-(decyloxycarbonyl)ethyl, 2-(ethoxycarbonyl)ethyl, 2-(propoxycarbonyl) Ethyl, 3-(methoxycarbonyl)propyl, 3-(ethoxycarbonyl)propyl and 4-(decyloxycarbonyl)butyl. In addition, the base may also have a 〇 135213.doc • 16- 200932735 CO 〇 unit. It is also possible that the CH2 group is replaced by only one group (carbonyl function). R1 and R2 in the formula I may each independently be an alkenyl group having 2 to 15 germanium atoms, wherein the CH2 group (preferably in the vicinity of the unsubstituted or substituted _C=C_ unit) is subjected to -co_, -C0_0_, _o_co_ or _o co o substitution wherein the group may be a straight chain or a branched chain. The group is preferably straight-chain and has 4 to 13 c atoms. Particularly preferred herein is propylene oxymethyl, 2-propene

Oxyl ethyl, 3, propylene oxypropyl, 4. propylene oxy butyl, % propylene methoxy pentylene [6 · propyloxy] hexyl, 7 - (tetra) decyloxyheptyl, 8- Propylene oxyoctyl, 9-propenyloxycarbonyl, mercaptopropyloxymethyl, 2-methylpropoxycarbonyl, 3·methylpropoxypropyl , 4-f-based acryloxybutyl, 5-methylpropenyloxypentyl, methylpropanyloxyhexyl, 7-methylpropenyloxyheptyl and 8-methacryl Alkoxyoctyl. Correspondingly, the -(:=(:__unit) near the alkynyl group

The 匸^ group can also be exchanged via _c〇-. -CO-〇_, -0-CO- or -〇_c〇_〇· wherein R1 and R2 in the formula I may each independently be an alkyl or alkoxy group having 1 to 15 germanium atoms or have 2 Alkenyl or alkynyl groups of up to 15 C atoms are each mono-substituted by -CN, and it is possible that these groups are substituted by -CN in any desired position in the oxime. And in the formula I and the ruler 2 may each independently be two or more CH 2 groups via -Ο- and/or -CO_〇_substituted alkyl' wherein the group may be straight or branched . It is preferably a branched chain and has 3 to atoms. R1 and R2 in formula I may each independently of each other be a decyl or decyloxy group having from 1 to 15 aryl atoms 135213.doc 200932735 or a dilute or alkynyl group having from 2 to 15 rainbow atoms, each of which is: F And CM and//Yang are mono- or polysubstituted, wherein the groups are preferably straight-chain and the halogen is preferably -F and/or _C. In the case of multiple substitutions, the dentate is preferably -F. The resulting group also includes perfluorinated groups such as an even group. Under a single substituted If / brother, the fluorine or gas substituent can be at any desired position, but preferably at the ω position. R and R2 in formula I may each independently be _F, _ci, I, 参, -SCN, -NCS or -SF5. In this case, the dielectric anisotropy increases to a larger positive value. These substituents should not be selected for particularly strong negative dielectric anisotropy. However, it is preferred for high ". Regarding the present invention, dentate means fluorine, gas, or moth, especially fluorine or gas. Regarding the present invention, unless otherwise stated in the specification or in the scope of the patent application Derogatory, otherwise the term "alkyl" means having 丨 to 丨5 (ie j, 2, 3, 4, 5, 6, 7, 8, 9, 10, u, 12, 13, 14 or 15) a linear or branched aliphatic hydrocarbon group of a carbon atom. If the alkyl group is a saturated group, it is also referred to as an "alkyl group." Particularly preferred is a form of the invention selected from the subtypes IA to IF. 〗 compound:

135213.doc • 18 - 200932735

The same meanings and the same preferred meanings as defined in the formula i may be the same or different meanings if A1 and A2 or Z1 and Z2 appear twice in the formulas IA to IF. IB1CIDIEIF has the following compounds in the following cases: 135213.doc •19· 200932735 About n+m=〇 Very particularly preferred compound is the following compound··

Wherein: R1, R2 are preferably shown above and below (F)p does not have an alkyl or alkoxy group of up to 8 C atoms. Part of the subform in each case

Wherein P represents 0, 1, 2, 3 or 4, and independently of each other, preferably represents a part of the following formula

Especially preferred

If the index P in the above and below formulas appears more than once 135213.doc, it may have the same or different meanings in the case of each occurrence of *20. 200932735, preferably 〇, 1 or 2.

A particularly preferred formula for n+m 1 is the following compounds:

Wherein: R1 and R2 have the same meanings as defined above. With respect to the pole of n+m=2, it is especially preferred that the compound of formula 1 A is the following compound

R2 135213.doc 200932735

R2 wherein: R1 and R2 have the same meanings as defined above. With regard to n+m=0, it is especially preferred that the compound of formula IB is the following compound:

135213.doc -22- 200932735 wherein: R1 and R2 preferably represent an alkyl or alkoxy group having up to 8 C atoms. With regard to n+m=1, it is especially preferred that the compound of formula IB is the following compound:

Wherein: R1, R2 and p have the same meanings as defined above. 135213.doc -23- 200932735

135213.doc • 24· 200932735

Wherein: R1, R2 and p have the same meanings as defined above. With regard to n+m=0, it is especially preferred that the compound of formula 1C is the following compound:

135213.doc -25- 200932735

Wherein: R1, R2 preferably represent an alkyl group or alkoxy group having up to 8 C atoms. With regard to n+m=1, it is especially preferred that the compound of formula 1C is the following compound:

135213.doc -26- 200932735 where: R1, R2 and p have the same meanings as defined above. It is especially preferred that the compound of the formula 1C is the following compound with respect to n + m = 2

135213.doc -27- 200932735

Wherein: R1, R2 and p have the same meanings as defined above. The most preferred compound of formula ID for n+m=0 is the following compound: 135213.doc -28- 200932735

R2

R2 where:

R1, R2 preferably denote an alkyl or alkoxy group having up to 8 C atoms. With regard to n+m=l, especially preferred compounds of the formula ID are the following compounds:

135213.doc -29- 200932735

R2 where: 0 R1, R2 and P have the same meanings as defined above. With regard to n+m=2, especially preferred compounds of the formula ID are the following compounds:

135213.doc -30- 200932735

135213.doc •31 - 200932735

Wherein: R R and p have the same meanings as defined above. The most preferable formula for n+m=〇 is the following compound

F F

among them

R1, R2 are preferably in the form of a group having up to 8 red atoms or a hospitaloxy group. The most preferred compound of the formula n+m=1 is the following compound:

135213.doc -32- 200932735

Wherein: R1, R2 and p have the same meanings as defined above.

With regard to n+m=2, especially preferred compounds of the formula IE are the following compounds:

135213.doc -33- 200932735

R2

135213.doc -34- 200932735

Wherein: R, R2 and p have the same meanings as defined above. The most preferable formula for n+m=〇 is the following compound

R2 wherein: R1, R2 preferably represent up to 8 (: an atomic alkyl or alkoxy group. With respect to n + m = 1 very particularly preferred formula if compound is the following compound:

F F

135213.doc •35- 200932735

Wherein: R1 and R2 have the same meanings as defined above. With respect to the pole of n+m=2, it is especially preferable that the compound is the following compound

R2

R2

R2 Φ

Wherein: R1 and R2 have the same meanings as defined above. If the group or substituent of the compound of the invention or the compound of the invention itself is in the form of an optically active or stereoisomeric group, a substituent or a compound due to, for example, an asymmetric center, (iv) is also encompassed by (4). Here 135213.doc -36- 200932735 It goes without saying that the compounds of the formula i of the invention may be in isomeric pure form (for example as pure enantiomers, diastereomers, E or Z isomers, trans or The cis isomer form) is present, or in a mixture of a plurality of isomers in any desired ratio (eg, racemate, E/Z isomer mixture, or cis/trans isomer mixture) presence. The M_cyclohexyl ring of the formula wherein the compound of the present invention and the other components of the liquid crystal medium are: preferably have a trans configuration, i.e., both substituents are in the equatorial position of the chair structure of the thermodynamically preferred structure. The compounds of formula I can be as documented (eg standard works such as H〇uben_)

The methods known per se in Weyl, Methoden der organischen Chemie [Methods of Organic Chemistry], Georg_Thieme_Verlag, plus morphines, are, in particular, prepared under the conditions known and suitable for such reactions. Changes that are known per se that are not mentioned in more detail herein can be used here. _ 'MB starting" is not separated from the reaction mixture and is immediately converted to a general oxime compound. The synthesis of the various compounds of the general formula i of the present invention is described by way of example in the examples. Substances may be obtained or are commercially available from commonly available literature procedures. The following is a description of the compounds of the invention, particularly 135213.doc-37·200932735 synthetic routes. The substituents R1, R2 in the following schemes are described below with reference to the schemes. , A1, A2, Z1, z2 and indices m and n have at least the meaning of formula I; R1 and R2 may also be selected from OTs (tosylate group) and OTf (triflate group), as the case may be. a derivatizable group of OMes (mesylate), -B(OH)2, -B(0-alkyl)2 or -B<(O-C2.10 alkylene-oxime). R" and R22 also have the meaning of such an extension of rW. Substituents A22 and Z22 are generally as defined for the groups A2 and z2, respectively; the code in the group -[Z22-A22]n-R22 is selected such that the group The closest group between -[Z22-A22]n-R22 and the tricyclic group generally conforms to the group of the formula -[Z2-A2]n-R2. The group of the formula -CH=CH_[z22_A22]n_R22 or the group of the formula -Ph-[Z22-A22]n-R22 is also formally intended to conform to the group of the formula -[Z2-A2]n-R2. Preferably, the compound of formula I is synthesized starting from compound 2 (see Scheme j). Using propargyl alcohol 3 (method j) [〇. Mitsunobu, • Sywi/zeib 1981, 1] or propargyl bromide 4 Method β) etherification of compound 2 to give the corresponding compound 5. Propargyl aryl ether 5 undergoes [3 3]_σ shift rearrangement when heated in iV, AT-diethylaniline to obtain a chromene derivative 6[H ishii, τ ishikawa, s S. Ueki, M. Suzuki, Chem. Pharm. Bull. 1992, 40, 1 148-1 153]. Final hydrogenation, followed by the target compound 1, which corresponds to the formula of the invention Compound I or an intermediate used in the preparation thereof.

135213.doc -38- 200932735

Scheme I: Synthesis of a compound starting from compound 2 This synthesis can be adjusted to suit the individual compounds of formula I by selecting the appropriate starting materials 2 and 3 or 4. Suitable block propanol 3 or propargyl desert 4 can be synthesized or synthesized by the disclosed methods. The synthesis of the starting material 2 is explained below with reference to some examples. If ring B in the compound of formula I represents a cyclohexyl group and if "and is equal to F, then the synthesis of compound 2 (or compound 2a herein) is initiated from compound 7, and the synthesis of compound 7 is disclosed in WO 2004/029015 A1 ( See process u) order. 135213.doc • 39· 200932735

7

1. LiTMP.THF f F

® Process II: Synthesis of Compound 2 (=2a) in which B = cyclohexyl and LkL^F is initiated by gasification of ruthenium (III) with the corresponding addition of Grignard (Grz_ or organic chemical compound) Functionalization of the initial β-tetralone 7 (see a) N. _ Takeda, T. Imamoto, Org. Synth. 1999, 76, 228-238. b) M.

Scommoda et al., /. Org. Chem. 1996, 61, 4379-4390) ° Elimination of the reaction by treatment with methanesulfonate and DBU (see M. Scommoda et al. above) to obtain a mixture of isomers Compound 9 of the main component. The materials are hydrogenated to give the corresponding tetrahydronaphthalene 10, which is subsequently converted to tetrahydronaphthalene by a reaction sequence of ortho-metallation and hydrolysis and in situ formation of the acid ester of 135213.doc -40-200932735. Phenol 2a. Ring B in the compounds of formula I of the present invention is intended to represent cyclohexenyl and if. Where both L2 are intended to be equal to F, the latter reaction sequence is carried out with intermediate 9 to give the corresponding starting material 2 (= 2c in Scheme VII). If the ring B in the compound of the formula I of the present invention represents a cyclohexyl group and if one of the substituents and/or L2 is equal to Η', the synthesis of the compound 2 is carried out starting from the compound. In L, L2 or L2 is preferably η, and the other substituent is f.

135213.doc -41 - 200932735 Scheme III: Synthesis of compound 2 (=2b) wherein B = cyclohexyl and lLH or F and L2 = H or F is similar to Scheme II, for which first promoted by ruthenium chloride (ΠΙ) The addition reaction of the corresponding Grenner or organolithium compound functionalizes the compound U(6-methoxynaphthalen-2-one) (see above). The elimination reaction (see above) is in turn obtained as compound i 3 as the main component in the mixture of isomers. This was hydrogenated to give 6-methoxy-1,2,3,4-tetrahydronaphthalene 14. Final use of boron tribromide to methyl ether

Cleavage (see a) J. F. W. McOmie, D. E. West, Co//.

Vol. V 1973, 412 ; b) E. H. Vickery, L. F. Pahler, E. J.

Eisenbraun, "/. Org. C/zew. 1979, 4444-4446) 〇 If ring B in compound 2 is intended to represent cyclohexenyl and if " and/or. If it is intended to be equivalent to hydrazine, intermediate 13 is used for cleavage of methyl ether to give the corresponding starting material 2 (= 2d in Scheme X). For the synthetic sequence shown in Scheme III, in the case where only one of the substituents or oxime 2 is equal to F and the remaining substituents are equal to hydrogen, the starting material 7-fluoro·6-methoxy-3 is required. , 4-dihydrohan-naphthalene_2_^lla (=Ll=F, l2=h and 8-fluoro-6-decyloxy-3,4-dihydro-1H-naphthalene-2__llb (=L〗= H, [2 = 1 to 11) (see Scheme 1v). These starting materials are also used in the method used in (4) 〇 15 A1, respectively, from 3 • fluoro_4_methoxy phenyl acetic acid 15 and 2-fluoro-4-methoxyphenylacetic acid 16 were prepared.

1. SOCI2 2·ethylene, AI〇3

F

Ο 11a 135213.doc 200932735

MeO

1. SOCI2 2. Ethylene, AICI3 HO 16

F

11b Scheme IV: Synthesis of 7·fluoro-6-decyloxy-3,4-dihydrogen//-naphthalen-2-one 11a and 8-fluoro-6-methoxy-3,4-dihydronaphthalene- 2-ketone lib. • M. Kuchaf Special (Collect, Czech. Chem. Commun. 1990, - 55, 296-306) has described the synthesis of 3-fluoro-4-methoxyphenylacetic acid starting from 2-fluoroanisole 15. 2-1-4-decyloxyphenylacetic acid 16 [S.-I. Sugita, S. Toda, T. Yoshiyasu, obtained by dimerization and ester saponification from 2-fluoro-4-hydroxyphenylacetic acid. a. Teraji, Mol. Cryst. Liq. Cryst. 1993, 237, 399-406; EJ Corey, JP Dittami, J. Am. Chem. Soc. 1985, 107, 256-257; Η. H. Wassermann, J. Wang, J. Org. Chem. 1998, W, 5581-5586]. Starting from 6-methoxy-3,4-dihydronaphthalene-2-one (11, where Li = L2 = H), a non-fluorinated synthetic building block 2 (where ι^ = Ε2 = Η) was obtained. The synthesis of 6-O methoxy-3,4-dihydrosheet-naphthalen-2-one (11, where L1 = L2 = H) has been described [SN Suryawanshi, SN Fuchs, 乂 (9rg. C/?ew· 1986, 57' 902-921]. Another particularly preferred synthesis of the product 2 is initiated from compound 17 or compound 18. The production of enol ether and its reaction with trifluoroacetic anhydride starting from 7. The reaction proceeds to the synthesis of hydrazine 17. A similar preparation of compound from compound 11 is shown in Scheme V). 135213.doc •43· 200932735

Scheme V: Synthesis of Compound 17 and Compound 18 The enol III II oleic acid vinegar 17 and 18 can be functionalized in a variety of ways in a transition metal promoted cross-coupling reaction [from (2/-<^/<3/ >^任<^〇01515- (A. de Meijre, edited by F. Diederich), Wiley-VCH, Weinheim, 2nd edition 2004] (see Flows VI and IX). Cross-coupling with A particularly preferred method for obtaining a functionalized dihydronaphthalene derivative 9 (formula) or 13 (formula): arylflusteric acid 19 (Suzuki coupling coupling), dilute oleic acid 21 and 23 [C_ Sun , R.

Bittman, J. Org. Chem. 2006, 7/, 2200-2202 and A. Torrado, S. Lopez, R. Alvarez, AR de Lera, Synthesis 1995, 285-293], other acid-free 25 [T. Oh- e, N. Miyaura, A. Suzuki, «/. C/zew. 1993, 55, 2201-2208], Grenner reagent 26 [B. Scheiper, M. Bonnekessel, H. Krause, A. Furstner, J. Org Chem. 2004, 69, 3943-3949]^. ^27 [Y. Zhao, K. Campbell, R.

R. Tykwinski, «/. C/zem. 2002, 67, 336-344]. In Scheme VI, some of the cross-coupling reactions of enol triflate sulfonate 17 are shown in the example 135213.doc -44- 200932735.

R

(ho)2b 21 [Pd〇], test

135213.doc -45- 200932735

R2

BrM g-^-Z?-A--R2 26

Fe(acac)3 or [Ni. 】

135213.doc -46- 200932735

Scheme v: an example of cross-coupling with enol triflate 17. The product 9 (formulae from Scheme XII) from this functionalization is again converted to the desired compound as shown in Schemes VII and VIII. 2 (see also Process II). BIf the B in the compound 1 of the present invention is intended to be a cyclohexenyl group, the compound 9 is converted to dihydronaphthalene 2C via a reaction sequence of orthometallation and hydrolysis and in situ formation of a oxidized reaction sequence of the p-benzoate. (See flow vil).

Scheme VII: Synthesis of Compound 2 (=2e) wherein β = cyclohexyl and li = l2 = F. If B in the compound 1 of the present invention is intended to be a cyclohexyl group, the compound 9 is first hydrogenated to give the compound 1 and Subsequent conversion to the corresponding tetrahydronaphthol 2a as above (see Scheme vilip

135213.doc -47- 200932735

Scheme VIII: Synthesis of Compound 2 (=2a) wherein B = cyclohexyl and lJ = L2 = F. Scheme IX shows some examples of cross-coupling reactions of enol triflate 18.

(琴jaki R22 21 [Pd〇], alkali 135213.doc -48- 200932735

135213.doc -49- 200932735 ❹

-R2

Scheme IX: Example of Cross Coupling with Enol Trisole 18 Further, the product 13 (formula) from this functionalization is converted to the desired compound 2 as shown in Scheme X and Scheme XI (see also the scheme). ΠΙ). If ring b in compound 2 is intended to represent cyclohexenyl and if L1 and/or L2 is intended to be equivalent to hydrazine, intermediate 13 is used for cleavage of methyl ether to give the corresponding starting material 2d (see Scheme X).

Scheme X: Synthesis of Compound 7 (=2d) in which Β = cyclohexenyl and L = H or F and L2 = H or F 135213.doc -50- 200932735 Right Ring σ 2 Ring B is intended to be _咕^ To express the hexyl group and if L1 and/or L2 is intended to be equal to H or F, then gas is obtained to obtain compound 14, followed by cleavage of methyl ether (see Scheme XI).

Scheme XI: Synthesis of compound 2 (=2b) wherein B = cyclohexyl and iJ = H or F and L2 = H or F. If ring B in the compound of formula I represents phenyl (L3 = H) or fluorinated phenyl ( L3 = F) (see Scheme XII) and if both L1 and L2 are equal to F, the synthesis is initiated from compound 33 (L3 = H or F) and the synthesis of compound 33 is disclosed in the literature by W〇® 2004/029015 A1. The intermediates 33 and the triflate 34 obtained therefrom (see Scheme XII) can be functionalized in a variety of ways (see Schemes XIII, Χϊν, and XV).

Scheme XII: Synthesis of trifluorodecanoate from compound 33 34 135213.doc 200932735 In the case of R2-(A2-Z2)n- intended to represent an alkoxy group, a simple ether of 33 using alkyl iodide or alkyl bromide (see Process XIII).

Scheme XIII: Etherification of Compound 33 to give compound 36 Another suitable method for the initial preparation of compound 33 (wherein L3 = H) from (2,3-difluorophenyl)ethyl hydrazine chloride is described in the literature [H. Juteau, Y. Gareau, Η.

Lachance, reira/zei/row Ze". 2005, 46, 4547-4549]. In this way, (2,3-difluorophenyl)ethethane gas is reacted with, for example, trimethylsulfonylalkylacetylene in the presence of vaporized aluminum (III) to give the corresponding 2-trimethylsulfonylalkylnaphthol . The decyl group is removed (e.g., using potassium fluoride in DMF), followed by compound 33. In the case of R2-(A2-Z2)n- intended to represent an alkenyl group, the triflate sulfonate 34 is reacted with the corresponding alkenyl acid in a palladium-catalyzed cross-coupling (see a) C. Sun, R. Bittmann, J. Org. Chem. 2006, 71, 2200-2202 b) A.

Torrado, S. Lopez, R. Alvarez, A. R. de Lera, Synthesis • 1995, 285-293). This alkenyl compound 37 can then be converted to the corresponding saturated compound 38 by hydrogenation (see Scheme XIV).

J-z^a^-R22

(h〇) 2b^ l Jn 21 [Pd. ], alkali 135213.doc -52- 200932735

Scheme XIV: Trifluorosulfonate 34 is coupled with an alkenyl acid and subsequently hydrogenated to provide compound 38. In addition, the transition metal-promoted triflate 34 is cross-coupled with, for example, the following to obtain a functionalized naphthalene. Particularly preferred methods for the derivative 39: aryl sun-acid (Suzuki coupling), terminal alkyne (coupling coupling) and Grenner reagent (wwadiz coupling or iron (III) promotion and coupling (See Scheme XV, which is shown here only for functionalization via coupling with Grenner reagents, for other possible functionalizations, see Scheme VI or Scheme IX).

Cross-coupling reaction (see Scheme VI and Scheme IX) For example BrMg+Z^-A^J^R2 26 Fe(acac)3 or [Ni°]

z-aHtr2 39 Scheme XV: Trifluorosulfonate 34 is functionalized by a cross-coupling reaction, which is shown here by way of coupling with a Grignard reagent. The functionalized naphthalene derivative 39 (formula) is then converted again to naphthol 2 (=2e) via an orthometallation reaction, a reaction sequence for the production of the acid ester and its hydrolysis and oxidation (see Scheme XVI). The process is continued with the naphthols 2 as shown in Scheme I. 135213.doc -53 - 200932735

Scheme XVI: Synthesis of a compound 2 (=2e) whose *B==phenyl, li=l2=F and L3=H or F

If ring B in the compound of formula I represents an unfluorinated phenyl group (l3=h) and if L1 and/or L2 is equal to hydrazine, wherein the substituent L1 or L2 which is not equal to η is preferably intended to be F, then from the compound Starting from 13 is the synthesis of compound 2 (here 2f) (see Scheme XVII). The synthesis of compound 13 has been presented above.

Scheme XVII: Synthesis of compound 2 (=2f) wherein B = phenyl, l1 = H or F and L2 = H or F and L3 = H 135213.doc • 54- 200932735 by treatment with bromine Conversion to the corresponding naphthol 4〇 (see w〇2004/029015 A1). The triflate 41 obtained from 40 can then be functionalized in a variety of ways as described above for 34 (see Scheme 及ι and Scheme XV). Scheme XVII only demonstrates the functionalization of 41 via Kumada coupling. As noted above, other reactions of triflate 41 are possible (see Scheme VI and Scheme IX). Methyl ether 42 is cleaved to give the starting material 2f required for further reaction (see Scheme I). Ο

In the case where R2-(A2-Z2)n- in 2f is intended to represent an alkoxy group, the synthesis should be modified. First, the method can be used in the final step of the synthesis of compound 7f (see Scheme XVII), which allows the aryl methyl ether to be in other alkyl aryl ethers (AK Chakraborti et al., /. C/iem. 2002, 67, 6406-6414 ; G.

Majetich et al., Tfeira/iei/row Le". 1994, 35, 8727-8730; E. Duran et al., /ieierocyc/e·? 2002, 5725-856) or aryl accompaniment (see Μ. T. Konieczny, G. Maciejewski, W. Konieczny, πί/ιαζ··? 2005, 1575-1577) in the presence of lysis. Another preferred method is shown in Scheme XVIII. Here, the synthesis of 2 g of the intermediate was carried out starting from bromotetralone 43. This material is in turn converted to the corresponding 6-bromonaphthalen-2-ol 44 [W〇 2004/029015 A1] by treatment with bromine, which can then be converted to the desired ether 46. Subsequent metallization with Mg, Grenner or organolithium compounds to cause further conversion to the desired naphthol 2g»

43 44 135213.doc -55· 200932735 XCR Factory f-Z^A^R22 45, (X = Br, I) R = (H, F, Cl)

1. Metallization reaction 2. B(OMe)3 3. H2〇2, HOAc

Scheme XVIII: Synthesis of compound 2 (=2g) wherein B = phenyl and l1 = h*f and l2 = h or F and L3 = H and r2-a2-z2 = alkoxy group 4 _Bromotoluene 47 starts with bromotetrahydrogen

Synthesis of naphthone 43 (see Scheme XIX, WO 2004/029015 Al; M_T. Konieczny et al., Price; 2005, 1575-1577; β P

Imbimbo et al., (10) 2〇〇s, material, 57〇5 572〇). 4_ desert-3-fluorofbenzene (47, L!=F </ L2=H) and 4-act-2-fluorotoluene (47, υ=Η, L2=F) are commercially available. The methyl bromide 47 is first brominated with NBS and the bromomethylene compound 48 is converted to the corresponding nitrile using potassium cyanide. These materials are then hydrolyzed to phenylacetic acid 49 which is subsequently converted to the desired bromotetralone 43.

V

Br~Κ 1)— NBS 135213.doc •56- 200932735 1. KCN, EtOH 2. NaOH, EtOH / H20

1 _ SOCI2 2. Ethylene, AICI3 Reference Process XIX: Synthesis of Substituted 4-Bromotetralone 43 Synthesis of Unfluorinated Synthetic Block 43 (Ι^=ΐ/=Η) by DM Tschaen et al , J. Org·· C/zeAn. 1995, (50, 4324-4330. If ring B in the compound of formula I represents a fluorinated phenyl group (L3=F) and if L1 and/or L2 is equal to Η, Substituents L1 or L2 which are not equivalent to hydrazine are preferably intended to be F, and it is also advantageous to carry out the combination of compound 2 (especially 2h and 2i) starting from bromo naphthol 44 (see Scheme XX and Scheme XXI).

135213.doc -57- 200932735 NEt3

OH

1. XCR2-[_Z21A?^-R^ (X = Br, I; R = H, F, Cl) 2. n-BuLi 3. B(OMe)3 4. H202, HOAc

Scheme XX: Synthesis of Compound 2 (=2h) wherein B = phenyl and LkH or F and L2 = H or F and L3 = F and R2-A2-Z2 = alkoxy

The naphthol 44 is first fluorinated using Selectfluor® (F-TEDA-BF4) to give difluoro-1H-naphthalen-2-one 50 (see WO 2004/029015 A1), which is subsequently reduced to 1H-naphthalene-2- Phenol 51. These materials are subjected to alkali treatment and then aromatized to obtain compound 52 while eliminating hydrogen fluoride. These compounds 52 are then also important intermediates for the synthesis of compounds wherein R2-A2-Z2 is intended to represent an alkoxy group (Scheme XX, final reaction). To this end, it is first etherified using a suitable alkyl complex and subsequently converted to naphthol for 2 h. Functionalization from trifluoromethanesulfonate 53 can be carried out starting from 52. In the cross-coupling using the various Grignard reagents shown (see Scheme XXI), there is a discriminating between the triflate and the bromo functional group [T. Kamikawa, T. Hayashi, Tetrahedron Lett. 1997, 35,7087-7090]. 54 turns 4 is naphthene 2i, and J further synthesizes the desired starting material 2 (especially 2i) (see Scheme I). 135213.doc -58- 200932735

54 1. n-BuLi 2. B(OMe)3 3. H202, HOAc

Scheme XXI - Synthesis of Compound 2 (= 2i) in which i is a B-local and L = H or F and L2 = h or FJ_ L3 = f

Is a compound of formula 1 wherein ring B represents an oxygen heterocycle. These compounds (4) (iv) Scheme I is prepared from the corresponding compound 2. If ring B in the compound of formula I represents an oxygen heterocycle and if. If both are equal to F, 7,8-difluorochroman-6-ol 2j is required as a starting material. These materials are synthesized starting from 2,3-difluorophenol (51) or 3,4-difluoro-2-hydroxybenzaldehyde (55) [a) NJ Lawrence, LA Hepworth, D. Rennison, AT McGown, JA Hadfield, J. Fluorine Chem. 2003, 123, 101-108. b) E. Marzi, J. Gorecka, M. Schlosser, Synthesis 2004, 1609-1618] (see Scheme XXII). -59- 135213.doc 200932735

1. PhNEt2, Δ

2. H2, Pd/C

Scheme XXII: Synthesis of Compound 2 (7,8-dioxfluorochroman-6-ol (2j)) in which B = piper and lLl^F, for this purpose, first by means of optical extension (Μ along σπσ 6 w) 2,3-difluorobenzene. (51) is reacted with propargyl alcohol 52 to give propargyl aryl ether 53 which undergoes a thermal [3.3]-σ shift rearrangement under suitable reaction conditions to give 2Η- Color ene. The chromene can be easily hydrogenated under mild conditions to give a corresponding color. Alternatively, the 7,8-difluorochroman 2j is from 3,4-difluoro-2-hydroxybenzaldehyde (55) [a) NJ Lawrence, LA Hepworth, D. Rennison, AT McGown, JA Hadfield, J Fluorine Chem. 2003, 123, 101- 135213.doc -60- 200932735 108 ; b) E. Marzi, J. Gorecka, M. Schlosser, Synthesis 2004, 1609-1618] via Petasis et al [a) NA Petasis, I. Akritopoulou, Tetrahedron Lett. 1993, 34, 583-586 ; b) NA

Petasis, IA Zavialov, J. Am. Chem. Soc. 1997, 119, 445-446 '» c) NA Petasis, IA Zavialov, J. Am. Chem. Soc. 1998, /20, 11798-11799] A reaction further developed by Wang and Finn [Q. Wang, MG Finn, Org. Leii. 2000, 2, 4063-4065] was obtained. In the presence of dibenzylamine, a 2,/, chromene such as 57 is obtained in a high yield from salicylaldehyde and vinyl-acid. This material can then be easily hydrogenated to give a corresponding color of 54 (see above). The intermediate 54 obtained in this manner is functionalized by ortho-metalation reaction and hydrolysis and in-situ oxidation of the acid ester to give 7,8-difluorochroman-6-ol 2j. If ring B in the compound of formula I represents a piper ring and if L1 is equal to F and L2 is equal to hydrazine, then compound 2 (especially 7-) is initiated starting from 5-bromo-4-fluoro-2-hydroxybenzaldehyde (58). Synthesis of fluorochroman-6-ol 2k). This starting material 58 can be selectively ortho-methylated from 3-fluorophenol by a method known in the literature [JB Blair et al, J. 2000, M, 4701-4710] and subsequently brominated [WA·Caroll et al. Person, 乂Met/. C/zew. 2004, 47, 3 163-3179] Obtained.

135213.doc -61 200932735

F H2i Pd/C

Scheme ΧΧΠΙ: Synthesis of compound 2 (=7-fluorochroman-6-ol 2k) wherein B = piper and lLf and L2 = H, advantageously from 5-bromo-4-fluoro-2-hydroxybenzalaldehyde (58) The synthesis was carried out by reacting with the above-mentioned ethylglycolic acid [Q. Wang, MG Finn, Ze &quot; 2000 2 4063-4065] followed by hydrogenation. After the halogen metal exchange, functionalization is carried out as described above to obtain a chromanol 2k. If ring B in the compound of formula I represents a piper ring and if l1 is equal to ^[and !^2 is equal to F, then compound 2 (especially 8-fluoro) is carried out starting from 2-fluoro-4-bromobenzene age (61) Synthesis of chroman-6-alcohol 21).

DEAD, PPh3

Z— 1. PhNE^A 2. H2( Pd/C~

Z2-a2士 R2 135213.doc -62· 63 200932735 F 1. Metallization reaction 2. B(OMe)3 3. H2〇2, HOAc

ZA^R2 Scheme XXIV: Synthesis of compound 2 (=8-fluorochroman-6-ol 21) wherein B = piperan and Ι/=Η and L2=F. The heterocyclic ring is preferably here by means of Claisen heavy The row is fused via propargyl aryl ether 62 (see Scheme XXIV). Functionalization was carried out using the same reaction sequence as that of the regioisomeric structure 2k to obtain a chromanol 21. Alternatively, the intermediate 2丨 can be synthesized via salicylaldehyde 64 starting from 2-fluoro-4-bromophenol (61) (see Scheme XXV). This can be obtained from 61 via Duff reaction [M. L. Micklatcher, M. Cushman, Synthesis 1999, 1878-1880]. It can then be followed by [Q. Wang, M. G.

Finn, Org. Lett. 2000, 2, 4063-4065] The procedure described by the household, followed by hydrogenation to carry out subsequent synthesis of the color full 63.

Scheme XXV: Synthesis intermediate 63 can also be synthesized by the above method (Claisen rearrangement or coupling with vinyl S-p-acid (hereinafter referred to as Pitts reaction)) wherein B represents a non-fluorine ring Compound of formula I (Ι^=Ι^=Η) (here especially la). In a particularly preferred method, a tricyclic structure is selectively formed by two consecutive Piteses reaction zones selected 135213.doc-63.200932735 (see Scheme XXVI).

OTBS

OH Br CHO 66

1. Br2, chci3 2. TBS-CI

H0^^~0H

CHO 65

(H〇) 2B

56 Bn2NH

2. H2, Pd/C

(H〇) 2B

3. TBAF.THF ^fz~ALtRl

56 Bn2NH

2, H2, Pd/C 1. n-BuLi, THF 2. N-mercaptopiperidine

R1-[-A1-Z1-j

z2—aHtr2

Scheme XXVI: Synthesis of Compound 1 (=la) wherein B = phenanthrene and lLlUh bromination and selective protection of 2,5-dihydroxybenzaldehyde (65) by means of methods known in the literature [Y. Hu , C. Li, BA Kulkarni, G. Strobel, E. Lokovsky, RM Torczynski, JA Porco, Org. Le&quot;. 2001, 3, 1649-165 2]. Chroma 67 was obtained by a first Pitts reaction followed by hydrogenation. Halogen-metal exchange, formazanization, and complete removal of the TBS protecting group are performed to obtain the acceptor 68 of the second Pittsson reaction. Finally, hydrogenation gives the target compound 1a. 135213.doc -64- 200932735 If the group RjAtiU- and/or R2[A2Z2]n- in the compound I is intended to contain an unsaturated group, bridge or ring system, the synthesis shown in Scheme I should be modified (see Process XXVII).

Method A: 1 MOM-CI, /-PrNEtg

OH 70 DEAD, PPh3

Scheme XXVII: Synthesis of a compound of formula I wherein the group / or R2_[A2_z2]n_ may contain an unsaturated group, bridge or ring system. According to the literature procedure [a) C. K. Bradsher, DC Reames, "/. Og. C/zem. 1981, #, 1384-1388 and b) LA Paquette et al., 乂 1994, 59, 2043-2051], from The compound of formula 71 is initially initiated to form a saturated rhodium-heterocyclic ring. To this end, compound 2 is first desertified in a suitable manner. In a preferred method (see Scheme XXVII, Method d), the MOM ether of Substance 2 is first prepared. These materials were selectively homogenized in the ortho position using gold n-butyllithium, and bromine was used to scavenge the organolithium compound. Finally, the MOM group is cleaved to give compound 69. And a) F. Mongin, M. Schlosser, Tetrahedron Lett. 1996, 37, 6551-6554; b) RC Ronald, MR Winkle, Tetrahedron 1983, 39, 2031-2042; c) MR Winkle, RC Ronald, J. Org Chem. 1982, 47, 2101-2108; d) M. Dabowski et al. » Tetrahedron 2005, 61, 6590-6595 or h. Coe, J. Chem. Soc. Perkin Trans. 1 1995, 2729-2737 The method similarly performs an orthometallation reaction. It can also be directly functionalized by treatment with bromine (see Scheme XXVII, Method B) (see a) CW Holzapfel, DBG Williams, Tetrahedron 1995, 51, 8555-8564; b) KJ Edgar, SN Falling, J. Org. Chem. 1990, 55, 5287-5291; c) R.

Johnsson, A. Meijer, U. Ellervik, Tetrahedron 2005, 61, 11567-11663). Etherification using bromopropanol derivative 70 gave compound 71. The organolithium compound obtained from the compounds (method d) or the Grignard reagent (method 5) obtained from the compounds spontaneously cyclize under the reaction conditions to form compound 1. The radical R2[A2Z2]n- suitable starting material 2 containing an unsaturated group, bridge or ring system can be obtained to a large extent as described above. It is only necessary to modify the synthesis of the compound in which ring B represents a cyclohexyl group and the compound in which ring B represents a piper ring. For compound 2 (especially 2a, 2c) wherein B represents a cyclohexyl group, the preparation of intermediates 10 and 14 can no longer be carried out starting from 8 and 12, respectively, via elimination, 135213.doc -66-200932735 hydrogenation ( See Process II and Process III). Thus, 10 and 14 were prepared directly from 8 and 12 by ionic reduction (see Scheme XXVIII).

Scheme XXVIII: Alternative Synthesis of Compounds 10 and 14 If it is intended to synthesize Compound 2 wherein 112 [22]11 contains an unsaturated group, bridge or ring system and B is intended to represent a piper ring, the following method is required (see Scheme XXIX). ).

135213.doc -67- 200932735

Scheme XXIX: Synthesis of the substituted color -6-alcohol 77 starting from sylphy 72 (Y=h, Br), using face acid 73 to form color thinner 74 [RA Batey, AN Avinash, AJ Lough, y Am, Chem s〇c 1999, (2), 450-451]. It is vaporized and oxidized to give an intermediate 75. Subsequent to this intermediate 75, a group R2[A2z2]n can be formed (e.g., by Vitig (fT/m'g)).

A method for functionalization to obtain a chroman-6-alcohol 77 has been fully described. With respect to the compound 1 in which B represents a fluorinated cyclohexane ring (here especially = lc) or the compound 1 in which B is a non-fluorinated cyclohexene ring (here especially = ld), wherein B is cyclohexene The following reaction sequence starting from the compound 1 of the ring (here especially = lb) is suitable (see Scheme XXX).

Where B is equal to the work of hexene z2-a2士 R2 135213.doc -68- 200932735

流程 Scheme XXX: synthesizing compound 1 (wherein lc in particular) wherein L1=H or F, L2=H or F and B=fluorinated cyclohexane and synthesizing Ι^=Η or F, L2=H or F And B = compound 1 of fluorinated cyclohexene (here especially Id)

The reaction scheme shown should be considered as illustrative only. Those skilled in the art will be able to carry out the corresponding modifications of the presented compositions and follow other suitable synthetic routes to obtain compounds of formula I. In accordance with the above-described synthesis, in one embodiment, the invention also encompasses one or more methods of preparing a compound of formula I. The invention thus encompasses a process for the preparation of a compound of formula J, characterized in that it comprises the following process steps, wherein a compound of the formula:

135213.doc -69- 200932735 where: η, A2 and Z2 are as defined above for formula i, and R22 is as defined for R1 and may additionally represent _〇Ts, 〇Tf, 〇Mes

Etherification on a hydroxyl group to give a compound of the formula:

Wherein m, η, A1, Z1, A2 and Z2 are as defined above with respect to the formula "Kg, and R22 is as defined with respect to R1 and may additionally denote _〇Ts, _〇Tf,

X represents -CH2CH2B1· or -CsCH, and Y represents deuterium or Br; and is cyclized at the groups X and γ, preferably obtaining the compound [compound. This cyclization is preferably carried out after the first method step. The product of this process is a compound of formula I or an intermediate suitable for the preparation of a compound of formula I. As already mentioned, the compounds of the formula I can be used in liquid-crystalline media. The invention therefore also relates to a liquid, crystalline medium comprising at least two liquid crystal compounds comprising at least one compound of the formula 。. The invention is also directed to liquid-crystalline media comprising from 2 to 40, preferably from 4 to 3, such components as other components than the various compounds of formula I of the invention. Such ribs particularly preferably comprise from 7 to 25 group wounds in addition to one or more compounds of the invention. These other components are preferably selected from the nematic or nematic nature (single 135213.doc 200932735

变性 to denaturing or isotropic) substances, especially from azobenzene, benzidine, diphenyl, terphenyl, 1,3_diπ, 2,5-tetrahydrofuran, benzoic acid Benzene vinegar or cyclohexyl benzoate, phenyl ester or cyclohexyl cyclohexane decanoate, phenyl or cyclohexyl cyclohexyl benzoate, phenyl ester of cyclohexyl cyclohexanecarboxylic acid or cyclohexan vinegar, benzoic acid Cyclohexyl phenyl ester, cyclohexyl phenyl cyclohexanecarboxylic acid or cyclohexyl phenyl cyclohexyl cyclohexane decanoic acid, phenylcyclohexane, cyclohexylbiphenyl, phenylcyclohexyl cyclohexane, ring Hexylcyclohexane, cyclohexylcyclohexylcyclohexene, 1,4-dicyclohexylbenzene, 4,4,2-dicyclohexylbiphenyl, phenylpyrimidine or cyclohexylpyrimidine, phenylpyridine or cyclohexylpyridine, benzene Dioxane or cyclohexyldioxane, phenyl-hydrazine, 3-dithiane or cyclohexyl-indole, 3-dithiane, 1,2-diphenylethane, 1,2-dicyclohexyl Ethane, 丨Phenyl-2-cyclohexylethane, 1-cyclohexyl-2-(4-phenylcyclohexyl)ethane, Cyclohexyl-2-phenyldiphenylethane, 1-phenyl- 2-cyclohexyl stupylethane, as appropriate, Phenyl ethers, tolans and substituted cinnamic acid of the class of substances. The 1,4-phenylene group in the compounds may also be monofluorinated or multi-gasified. The most important compounds of the other components suitable for use as the medium of the present invention can be represented by formulas (II), (III), (IV), (V) and (VI): R'-LE-R&quot; (II) R'- L-COO-E-R&quot; (III) R'-L-OOC-E-R&quot; (IV) R'-L-CH2CH2-E-R&quot; (V) R'-L-CF20-E-R&quot; (VI) L-Cyc- '-Phe-Phe- which may be the same or different. In the formulas (II), (III), (IV), (V) and (VI) and E, each independently represents from 135213 .doc •71 - 200932735 y CyC&quot;GyC' ' 'pyr- ' -Di〇~ ' -Thp- ' -G-Phe- and · and its mirror-formed group of divalent bases, where Phe means unsubstituted Or substituted by oxygen 1 &gt; 4 • Stupid base, Cye means Μ Μ 环 或 或 ^ ^ ^ Pyr Pyr Pyr Pyr Pyr Pyr Pyr Pyr Pyr Pyr Pyr Pyr Pyr Pyr Pyr Pyr Pyr Pyr Pyr Pyr Pyr Pyr Pyr Pyr Pyr Pyr Pyr Pyr Pyr Pyr Pyr Pyr Pyr Pyr Pyr Pyr Pyr Pyr Pyr Pyr Pyr Pyr _2,5_diyl, Thp represents tetrahydropyrano-2,5_diyl and G represents 2·(trans-1,4_cyclohexyl)ethyl, biting _25 diazetidine-2,5 a mono-, 1,3-dioxane-2,5-diyl or tetrahydropyran-2,5.diyl.

One of the groups L and oxime is preferably Cyc or Phe. Preferably, Ε is Cyc, Phe or Phe-Cyc. The medium of the present invention preferably comprises one or more groups selected from the group consisting of compounds of the formula (ΙΙ), (ΠΙ), (IV), (v) and (VI) selected from the group consisting of Cyc and Phe. And at the same time comprising one or more selected from the group consisting of one of the groups 1 and e selected from the group consisting of Cyc and Phe and the other group selected from -Phe-Phe-, -Phe-Cyc., -Cyc -Cyc-, -G-Phe- and -G-Cyc-groups of the compounds of formula (II), (III), (IV), (v) and (VI), and optionally one or more From the group (π), (in), (IV), (wherein the groups L and E are selected from the group consisting of -Phe-Cyc-, -Cyc-Cyc-, _G-Phe-, and -G-Cyc- The components of the compounds V) and (VI). In a smaller subgroup of compounds of formula (II), (III), (IV), (V) and (VI), R' and R&quot; each independently represent a decyl group, alkene having up to 8 C atoms Alkyl, alkoxy, alkoxyalkyl (oxaalkyl), alkenyloxy or decyloxy. This smaller subgroup is hereinafter referred to as Group A, and the compounds are represented by the subtypes (Ila), (Ilia), (IVa), (Va) and (Via). In most of these compounds, R' and R&quot; are different from each other, and one of the groups is usually an alkyl group, an alkenyl group, an alkoxy group or an alkoxyalkyl group (oxaalkyl). 135213.doc -72- 200932735 In another small subgroup of compounds of formula (II), (III), (IV), (V) and (VI), which is referred to as group B, E means:

F F

In the compounds of group B represented by the sub-formulas (lib), (Illb), (IVb), (Vb) and (VIb), 'R, and R' are as defined for the compounds of the formulae (IIa) to (VIa). Defining and preferably an alkyl, alkenyl, alkoxy or alkoxyalkyl group (oxaalkyl). In the compounds of formula (II), (III), (IV), (V) and (VI) In another smaller subgroup, 'R&quot; denotes -CN. This subgroup is hereinafter referred to as group C, and the compounds of this subgroup are correspondingly subclasses (lie), (IIIc), (IVc), (Vc) and (VIc) describes that in the compounds of the formulas (lie), (IIIc), (IVc), (Vc) and (VIc), R' is as defined for the compounds of the formulae (Ila) to (VIa) and Preferred are alkyl, alkenyl, alkoxy or alkoxyalkyl groups (oxaalkyl®, other compounds other than the preferred compounds of groups A, B and C, having other variations of the extracted substituents (ΙΙ), (ΙΠ), (IV), (V) and (VIHb compounds also

The method is obtained.

The weight ratio of the compound to the group is: Group A: 135213.doc • 73· 200932735 0 to 90%, preferably 20% to 90%, especially 30% to 90%. Group Β : 0 to 80%, preferably 10% to 80%, especially 10°/. Up to 70%. Group C: 0 to 80%, preferably 5% to 80%, especially 5% to 50%. The medium of the present invention preferably comprises from 1% to 40%, particularly preferably from 5% to 30%, of the compound of the formula I of the present invention. The medium preferably comprises one, two, three, four or five compounds of the formula I according to the invention. Examples of the compounds of the formulae (II), (III), (IV), (V) and (VI) are the compounds shown below:

135213.doc •74- 200932735

135213.doc •75- 200932735

Wherein Ra, ... independently of each other represents -CpH2p + 1 or -OCpH2p+i, and p = 1, 2, 3, 4, 5, 6, 7, or 8, and L1, L2 independently of each other - Η or -F ,

F -76- 135213.doc 200932735 -coo

CmH 2m+1

CnH2n+1 -c2H4-

-CmH 2m+1 ^η^2η+Γ -C2H4-

CmH2j :m+1

❹ CnH2n+T CH2〇-CmH2m+1

^n^2rvH

CmH2m+i

F F

135213.doc -77- 200932735

Wherein m and 11 independently represent 1, 2, 3, 4, 5, 6, and 7 Ge8. The media of the present invention are prepared in a manner known per se. In general, it is preferred to dissolve the components in the other at a high temperature. The liquid crystal phase of the present invention can be modified by means of a suitable additive to make it usable in all types of liquid crystal display elements which have been disclosed so far. Additives of this type are known to those skilled in the art and are described in detail in the literature (H. Kelker/R Hatz,

Handbook of Liquid Crystals, Verlag Chemie, Weinheim, 1980). For example, a pleochroic dye can be added to produce a colored guest-host system or an additiveizable material to alter the dielectric anisotropy, viscosity, and/or alignment of the nematic phase. The compounds of formula I are especially suitable for use in VA_TFT displays due to their negative Δε. The present invention is therefore also directed to an electro-optical liquid crystal display element comprising the liquid crystal medium of the present invention. Other combinations of embodiments and variations of the invention may be derived from the scope of the claims. [Embodiment] 135213.doc •78- 200932735 The present invention will be described in more detail below with reference to working examples, but is not intended to be limited thereby. Those skilled in the art should be able to discover from these examples the details of the work not detailed in the general description, generalize it based on general expertise and apply it to specific problems. In addition to the commonly used and well-known abbreviations, the following abbreviations are also used: C. Crystal phase, N. Nematic phase, Sm. Smectic phase, I. Isotropic phase. The numbers between the symbols show the transition temperature of the substance. Temperature data is in degrees Celsius (°C) unless otherwise stated. Physical, physicochemical or electro-optical parameters are generally known methods as described in the booklet &quot;Merck Liquid Crystals-Licristal®-Physical Properties of Liquid Crystals-Description of the Measurement Methods&quot;, 1998, Merck KGaA, Darmstadt Determination. Above and below, Δη represents optical anisotropy (589 nm, 2(TC) and Δε represents dielectric anisotropy (1 kHz, 20 ° C). Dielectric anisotropy Δ ε is at 20 ° C and The optical anisotropy Δη is measured at a wavelength of 20 ° C and 589.3 nm. The Δε and Δη values and the rotational viscosity (γι) of the compound of the present invention are 5% to 10% of the individual inventions. Compound and 90%-95% of commercially available liquid crystal mixture ZLI-285 7 (for the determination of Δε) or ZLI-4792 (for the determination of Δη, 丫丨8 mixture, Merck KGaA, Darmstadt) liquid crystal mixture linearly extrapolated The abbreviation has the following meanings: DIAD diisopropyl azodicarboxylate 135213.doc -79- 200932735 MTBE decyl tertiary butyl ether THF tetrahydrofuran DMF dimethylformamide in vac. in vacuum (about 1 〇 -2 bar) sat. Saturated «-BuLi n-butyllithium, solution in hexane Mes sulfonyl hydrazine-based MOM hydroxy fluorenyl O RT room temperature F-TEDA-BF4 1- gas fluorenyl-4-fluoro -1,4-diazabicyclo[2.2.2]octane ditetrafluoroborate TMP 2,2,6,6-tetradecyl brigade bite dppp 1,3-bis(diphenylphosphino)propane Tf Trifluoro Sulfonyl Ts Benzene sulfonyl sulfonyl NMP N N - fluorenyl-2 - ° ratio 1 biting example Starting materials can be obtained according to generally available literature procedures or are commercially available. Example 1: 5,6-II Fluor-3-(4-propylcyclohexyl)-1,2,3,8,9,10-hexahydro-pyran

And [3,2-f]chromene -\ / -\ F F 135213.doc -80- 200932735 Preparation of 1,2-fluoro-3-prop-2-ynyloxybenzene

115.0 g (〇.88 mol) of 2,3-difluorophenol with 118 2 ml (17 7 mol) propargyl bromide (80% solution in toluene) and 146.6 g (l38.2 mol) potassium carbonate The mixture was refluxed for 3 hours in 1.6 1 ethyl methyl ketone. The batch was filtered and the residue was filtered with EtOAc. The filtrate was evaporated to dryness and the residue was purified mjjjjjjjjjj 1-2 Preparation of 7,8-difluoro-2孖-chromene

73.0 g (0.43 difluoro_3_prop-2-ynyloxybenzene) together with 126 g (2.17 mol) potassium fluoride in an autoclave in 65 such as N,N-diethylaniline at 200 The mixture was heated for 3 hours at ° C. Water was added to the batch of towels, followed by acidification using 25 Torr. hydrochloric acid. The solution was extracted with MTBE and the combined organic phases were washed with saturated sodium sulphate solution. It was evaporated to dryness. The residue was purified by column chromatography (Si.sub.2, n-heptane: MTBE=l?: i). In this way, 7,8-difluoro-2//_ a mixture with the starting material 1,2-difluoro-3-prop-2-ynyloxybenzene. 1.3 Preparation of 7,8-difluorochrome 135213.doc -81 - 200932735

Mixture of 78_diox_2//_ dilute with 12 dioxane·2·fast oxybenzene (43.2 g) in the presence of Pd/C (5% Pd) at room temperature at 43 G ml Hydrogenation in THF for 1 hour. The batch was evaporated to dryness, and the crude product was purified by column chromatography (Si〇2 'Zhengwuyuan: 丨·气丁院=4:1) to obtain pure 7,8-difluorocarbon as a pale yellow liquid. Full color. 1.4 Preparation of 7,8-difluorochroman _6-alcohol

1. n-BuLi 2. B(OMe)3 3. H202i H〇Ac

81.2 ml (0.13 mol) «-BuLi (15% solution in hexane) was added to 20.0 g (〇.l2 mol) of 7,8-difluorochrome in 400 ml of THF at -7 °C. In solution. After 3 hours at this temperature, 丨 4.4 ml (0.13 mol) of trimethyl ester ’ was added dropwise and the batch was warmed to room temperature. 3 〇 ml of dilute acetic acid (about 30%) was added and 30 ml of aqueous hydrogen peroxide (35%) was carefully added to the batch. After the addition was completed, the mixture was stirred at room temperature for 7 hours. Water was added and the batch was acidified using 2 N hydrochloric acid. The solution was extracted several times with MTBE, and the combined organic phases were washed successively with water, a saturated sodium chloride solution and an ammonium ferric sulfate solution. The solution was dried using sodium sulfate and evaporated to dryness. The crude product was purified by column chromatography (SiO 2 , n-heptane: MTBE = 2:1). 1.5 Preparation of 7,8-difluoro-6-[l-(4-propylcyclohexyl)prop-2-ynyloxy] color 135213.doc -82 - 200932735

Initially 5.0 g (26.9 mmol) of 7,8-difluorochroman-6-ol with 5.33 g (29.6 mmol) of 1-(4-propylcyclohexyl)prop-2-yn-1-ol and 8.45 g ( 32.2 mmol) Triphenylphosphine was introduced together into 65 ml of THF, and 6.79 ml (34.9 mmol) of DIAD was added over 30 minutes under ice cooling. The semi-saturated gasification solution was added after 19 hours at room temperature, and the mixture was extracted multiple times with MTBE. The combined organic phases were washed with water and a saturated sodium carbonate solution and dried over sodium sulfate. The residue remaining after removal of the solvent was purified by column chromatography (Si.sub.2, n-pentane. MTBE=2:1) to afford 7,8-difluoro-6-[l- (4-propylcyclohexyl)propan-2-alkynyloxy] is full. 1.6 Preparation of 5,6-difluoro-8-(4-propylcyclohexyl)_1,2,3,8-tetrahydropyrano[3,2-f]chromene F p

135213.doc -83- 200932735

F F

PhNEt2, Δ 6.0 g (17.2 mmol) of 7,8-difluoro-6-[l-(4-propylcyclohexyl)prop-2-ynylyl)-color and 2.0 g (34.4 mmol) The mixture was heated together at 55 ° C for 6 hours in 55 ml of N,N-diethylaniline. After cooling, water was added and the mixture was acidified using 25% hydrochloric acid. The batch was extracted with MTBE and the organic phase was washed with a saturated sodium hydride solution. The solution was dried using sodium sulfate and evaporated to dryness. Purification of the crude product by column chromatography (Si.sub.2, 1-hexanes) to afford 5,6-difluoro-8-(4-propylcyclohexyl)·1,2 as a light brown oil. 3,8-tetrahydrogen thio[3,2-£'] color thin. I,7 Preparation of 5,6-difluoro-3·(4-propylcyclohexyl)4,2,3,8,9,10-hexahydropyrano[3,2-f]chromene

F F

H2. Pd/C

4 〇g (11.5 mmol) of 5'6-difluoro-8-(4-propylcyclohexyl)8-tetrahydroperoxide in THF at atmospheric pressure and in the presence of pd/C (5.% Pd) The fused [3,2-f] chromene hydrogenation. The reaction solution was filtered, and the filtrate was evaporated to dryness. The residue was purified by column chromatography (Si 〇 2 </RTI> &lt;RTI ID=0.0&gt; Further purification by repeated recrystallization from n-heptane at 5 ° C afforded 5,6·difluoro_3_(4-propylcyclohexyl 135213.doc-84- 200932735 1, as a colorless solid. 2,3,8,9,1 0-hexahydro britylene [3,2-f] chromene (melting point 1 52. 〇).

△ ε=-10.4 △ η=0.0663

C 152 I © lH_NMR (250 MHz, CHC13): δ=4.23-4.07 (m,2H,8-H), 3.68-3.61 (m,1H,3-H), 2.62-2,39 (m,4H, Hm), 2.09-1.97 (m, 4H, H-fat), 1.85-1.73 (m, 4H, Η**), 1.71-1.50 (m, 1H, H&quot;), 1.40-1.25 (m, 2H, H Aliphatic),! 22-1.03 (m, 4H, H* family), 0.99-0.81 (m, 6H, family) 〇i F-NMR (235 MHz, CHC13): δ=-ΐ6ΐ.8 (d,1F, JT=19.5 Hz ), -162.2 (d, 1F, J = 19.5 Hz). MS (El): m/e (〇/〇) = 350 (1〇〇, M+) 〇 Example 2: 5,6-difluoro-3_pentyl-8-(4-propylcyclohexyl)4, 2,3,8,9,i〇-hexahydropyrano[3,2-f]chromene

2.1 Preparation of 1-(1-ethynylhexyloxy)_2,3-difluorobenzene 135213.doc -85- 200932735

Initially, 2.4 g (0.33 mol) of 2,3-difluorophenol was combined with 50.0 mi (〇34 mol) of 1-octyne-3-ol and 94.1 g (〇.36 mol) of triphenylphosphine. i

A solution of 76.1 ml (〇.39 mol) DIAD in 1 mL of THF was added dropwise in THF. After 19 hours at room temperature, the batch was diluted with MTBE and washed with water. The aqueous phase was extracted with MTBE and the combined organic phases were washed with a saturated sodium carbonate solution. The solution was dried using sodium sulfate and evaporated to dryness. The residue was purified by column chromatography (yield: EtOAc) to afford 1-(1-ethynylhexyloxy)-2, 3-difluorobenzene as a colorless oil. 2.2 Preparation of 7,8-difluoro-2-pentyl-2H-chromene

62·〇 g (〇.26 mol) of 1-(l-ethylhexyl hexyloxy)-2,3-difluorobenzene in 390 ml of N,N-diethylaniline at 195. Heat underarm for 2 hours. The batch was diluted with MTBE. 1 Wash the strip multiple times with 1 N HC1. The organic phase was dried over sodium sulfate and evaporated to dryness. The residue was purified by column chromatography (jjjjjjjjjjjjjj 2.3 Preparation of 7,8-diindole-2_pentyl color 135213.doc -86 - 200932735

M〇l) 7,8-two ° steaming the batch at room temperature in the presence of Pd / C (5% Pd) 51.0 g (〇21 fluoro-2-pentyl-2 / / - 浠 510 Hydrogenation of ml hydrazine for 1 hour to dryness: the crude product (yellow liquid) can be used directly in the next step to prepare 7,8-difluoro-2-pentylchroman-6-ol

1. n-BuLi 2. B(OMe)3 3. H2〇2, HOAc

Initially, 52.4 g (about 0.22 mol) of crude 7,8-difluoro-2-pentyl was introduced into 400 ml of THF, and 150.7 ml (0.24) was added at -70 °C.

BuLi (15% solution in hexane). After 3 hours at this temperature, 26.8 ml (〇.24 mol) of tridecyl borate was added dropwise, and the batch was warmed to room temperature. Add 55 ml of dilute acetic acid (about 30%) and add 57 ml of hydrogen peroxide solution (35%) to the batch. After the addition was completed, the mixture was allowed to stand at room temperature for 17 hours. Water was added and the batch was acidified using HCl. The combined organic phase was washed with a plurality of MTBE extraction solutions' and sequentially with water, a saturated sodium hydride solution and an iron (II) sulfate solution. The solution was dried using sodium sulfate and evaporated to dryness. The crude product was purified by column chromatography (Si 〇 2, n-heptane: MTBE = 2:1). 2.5 Preparation of 7,8-difluoro-2-pentyl-6-[ 1-(4-propylcyclohexyl)prop-2-ynyloxy] Colour 135213.doc -87- 200932735

F F

F F

Initially 8.0 g (31.2 mmol) of 7,8-difluoro-2-pentylchroman-6-ol and 6.75 g (37.4 mmol) of 1-(4-propylcyclohexyl)prop-2-yn-1-ol 9.83 g (37.6 mmol) of triphenylphosphine was introduced into 75 ml of THF, and 7.89 ml (40.6 mmol) of DIAD was added over 30 minutes under ice cooling. After 20 hours at room temperature, a half-saturated sodium vapor solution was added and the mixture was extracted multiple times with MTBE. The combined organic phases were washed with water and a saturated sodium carbonate solution and dried over sodium sulfate. The residue remaining after removal of the solvent was purified by column chromatography (Si.sub.2, n-pentane: MTBE=2:1) to afford 7,8-difluoropentyl-6-[ 1_(4-propylcyclohexyl)prop-2-ynyloxy] is full. 2.0 Preparation of 5,6-difluoro_3_pentyl-8_(4-propylcyclohexyl)tetrahydrofuran [3,2-f] chromene

F P

135213.doc 200932735 9.7 g (23.2 mmol) of 7,8-difluoro-2-pentyl-6·[1-(4-propylcyclohexyl)prop-2-ynyloxy] is saturated with 2.7 g (46.5 mmol) potassium fluoride was heated together in 75 ml of N,N-diethylaniline at 200 ° C for 6 hours. After cooling, water was added and the mixture was acidified using 25% hydrochloric acid. The batch was extracted with MTBE and the organic phase was washed with a saturated sodium carbonate solution. The solution was dried using sodium sulfate and evaporated to dryness. The crude product was purified by column chromatography (EtOAc, EtOAc: EtOAc: EtOAc: 4-propylcyclohexyl)-^tetrahydropyrano-pyrochromene. 2.7 Preparation of 5,6-difluoro-3-pentyl-8-(4-propylcyclohexyl)-1,2,3,8,9,10-hexahydropyrano[3,2-f] Alkene

5,6-difluoro-3-pentyl-8-(4-propylcyclohexyl)-1 will be obtained in THF at atmospheric pressure and in the presence of pd/c (5% pd). 2,3,8-four = Chen Wei and color (four). The reaction solution was passed through and the solution was evaporated to dryness. By column chromatography (si〇2'-gengyuan: *,, the residue was purified by left-right τ a residue by recrystallization from n-heptane at 5 C to give a colorless solid. _ _ P, J 戌丞 -8- (4- propyl hexyl) -1, 2, 3, ϋΐ〇 _ Α # n preparative HPLC to enter ^ [3, 2 _ f] color thin. For example, borrow Further separation of the resulting mixture of diastereomers by hydrazine 135213.doc -89 - 200932735. Isomer 1 (melting point 128 ° C):

Δε=-11.2 ' Δη=0·0742

❹ C 128 I !H-NMR (500 MHz, CHC13): 8=3.94-3.90 (m, 1H, 8-H), 3.67-3.64 (m, 1H, 3-H), 2.60-2.54 (m, 2H , H Gr), 2.48-2.41 (m, 2H, 2.06-1.99 (m, 3H, Hmm), 1.82-1.68 (m, 6H, H®), 1.61-1.49 (m, 4H, Η®) , 1.46-1.40 (m, 1H, H® family), 1.35-1.28 (m, 6H, family), 1.26-1.07 (m, 4H, H aliphatic), 0.96-0.87 (m, 8H, family). 19F - NMR (235 MHz, CHC13): δ = -163.1 (m, 2F) ❿ MS (El): m/e (%) = 420 (100, M+). Isomer 2 (melting point 131 ° C):

Αε--9.2 Δη=0.0894

C 131 I 135213.doc -90- 200932735 ^-NMR (500 MHz, CHC13): 6=3.91-3.86 (m, 1H, 8-H), 3.65-3.61 (m, 1H, 3-H), 2.53- 2.49 (m, 4H, Hm*), 2.06-2.00 (m, 3H, H» family), 1.83-1.66 (m, 6H, family), 1.62-1.50 (m, 4H, Η» family), 1.47-1.40 (m, 1H, H mill), 1.38-1.28 (m, 6H, H®*), 1.26-1.07 (m, 4H, H aliphatic), 0.97-0.87 (m, 8H, H aliphatic). 19F-NMR (235 MHz, CHC13): δ = -163·8 (m, 2F). MS (El): m/e (%) = 420 (100, M+). Example 3: 5,6-Difluoro-3-pentyl-8-propyl-1,2,3,8,9,10-hexahydro-deutero[3,2-f]chromene

F F

CsH,,

3.1 Preparation of 6_(1·ethynylbutoxy)-7,8-difluoro-2-pentylchroman

Initially 10.0 g (39.0 mmo)) 7,8-difluoro-2-pentylchroman-6-ol with 4.0 g (41.0 mmol) of 1-hexyn-3-ol and 11.3 g (42.9 mmol) of triphenyl The phosphine was introduced together in 140 ml of THF, and 9.1 πι1 (46·8 mmol) DIAD was added over 20 minutes under ice cooling. After 18 hours at room temperature, water was added and the mixture was extracted multiple times with MTBE. The combined organic phases were washed with water and a saturated sodium hydride solution, and dried over sodium sulfate. Purification by column chromatography (Si〇2 'n-heptane: ΜΤΒΕ=2··1). Residue remaining after removal of solvent 135213.doc •91 - 200932735 ''A yellow oily 6-(1 -ethynylbutoxy)_7,8-difluoro-2-pentyl color. 3.2 Preparation of 5,6-difluoro-3-pentyl-8-propyl-1,2,3,8-tetrahydrofuran [3,2_f] chromene

9.0 g (26.8 mmol) of 6-(l-ethynylbutoxy)_7,8.difluoro-2-pentyl was added to 90 ml of hydrazine, and hydrazine diethylamine was heated at 205X: for 3 hours. The batch was diluted with hydrazine and washed several times with 3 N HCl. The organic phase was dried over sodium sulfate and evaporated to dryness. The residue was purified by column chromatography (EtOAc, EtOAc (EtOAc: EtOAc): , 2,3,8-tetrahydropyrano[3,2-f]chromene. 3-3 Preparation 5,6-*---3-mercapto-8-propyl-1,2,3,8,9,10-hexazapyrano[3,2-f]

8.0 g (23'8 mm〇l) 5,6-difluoro-3-pentyl-8-propyl-1 in toluene at atmospheric pressure and in the presence of Pd/c (5〇/〇Pd) , 2,3,8_ Tetrahydropyrano[3,2-f]chromene was hydrogenated for 5 hours. The reaction solution was filtered, and the filtrate was evaporated to dryness. The residue was purified by column chromatography (Si 〇 2, n-heptane: 丨·············································· A 1:1 mixture of 5,6-difluoro-3-pentyl-8-propyl-1,2,3,8,9,10-hexahydropyrano[3,2-f]chromene. This material is resolved, for example, by preparative HPLC. Isomer 1 (melting point 84 ° C):

Δε=-10·2 φ Δη=0.0463

Γ1=295 mPa·s C 84 I ^-NMR (500 MHz, CHC13): 6=3.92-3.80 (m, 2H, 3-H, 8-H), 2.57-2.33 (m, 4H, H»^) , 2.02-1.91 (m, 2H, H"), 1.76-1.60 (m, 4H, Hu), 1.57-1.36 (m, 8H, H* family), 1.33-1.17 (m, 6H, He), 0.93-0.78 (m, 6H, family) 19F-NMR (235 MHz, CHC13): δ=-163.4 (s, 2F) ❹ MS (El): m/e (0/〇)=338 (100, M+) Isomer 2 (melting point 61 ° C):

Δε=-11.8 Δη=0.0464 γι=488 mPa · s 135213.doc -93- 200932735

C 61 I !H-NMR (500 MHz, CHC13): δ = 3.92-3.84 (m, 2H, 3-H, 8- H), 2.56-2.48 (m, 4H, H"), 2.O8-I .99 (m, 2H, H La), 1.84_ 1.66 (m, 4H, H), 1.64-1.41 (m, 8H, h), 1.36-1.29 (m, 6H, H*) , 0.97 (t, 3H, J = 7.2 Hz, Me), 0.90 (t, 3H, J = 7.i

Hz, Me) 0 Example 4: 5,6-difluoro-3-propyl-8-(4-propylcyclohexyl)_2,3,7,8,9,l-hexahydro-1H-benzo [f]chromene

F F

4.1 Preparation of trifluoromethanesulfonic acid 7,8-difluoro-3,4•dihydronaphthalene-2-yl ester

φ 54.0 g (1·35 mol) of sodium cyanide (6 〇% suspension in paraffin oil) was washed with pentane and suspended in 1.25 1 diethyl ether. Slowly suspend the solution of 12〇.〇§(〇.60 111〇1) 7,8-monofluoro-3,4-dihydro-///-naphthalene-2-one in 75〇ml In the liquid, and after the addition was completed, the batch was stirred at room temperature for 3 minutes. The mixture was cooled to hydrazine.匚, and add 12 〇 〇 ml (〇 71 m〇1) of difluoroacetic anhydride dropwise. After the addition was completed, the batch was stirred at 0 ° C for 2 hours and added to dilute hydrochloric acid. use! The mixture was extracted several times and the combined organic phases were washed with a saturated sodium carbonate solution. The solution was adsorptively filtered (Si〇2 ' MTBE) and the filtrate was evaporated to dryness. The residue was treated with n-heptane: phenyl 135213.doc • 94- 200932735 = 7:3, and the organic phase was separated. The solution was evaporated to dryness, and the residue was purified by column chromatography (Si2, n-heptane: toluene = 7:3) to give a trifluoromethanesulfonic acid 7,8-difluorobenzene as a yellow oil. _3,4_Dihydronaphthyl vinegar. 4.2 Preparation of 5,6-difluoro_3-(4-propylcyclohexyl)_1,2-dihydronaphthalene

9.0 g (28.6 mmol) of trifluorosulfonium was initially acidified at -30 C. 7,8-difluoro 3,4-azepine-2-ylg was 550 mg (1.55 mmol) Fe(acac)3 And 3 〇 ml of NMP was introduced into 5 〇〇mi THF. A solution of 3,5 g (0.15 mol) of 4-bromopropylcyclohexane and 3 6 g (〇 15 m〇1) of magnesium turnings to produce 4 propylcyclohexylmagnesium bromide in 3 50 ml of diethyl ether was quickly added. After the addition was completed, the mixture was stirred at -30 ° C for 30 minutes and added to a saturated ammonium sulfide solution. The mixture was extracted several times with MTBE, and the combined organic phases were washed with a saturated sodium carbonate solution. The solution was dried using sodium sulfate and evaporated to dryness. The residue was purified by column chromatography (EtOAc EtOAc EtOAc) 4.3 Preparation of 7,8-fluoro-2-(4-propylcyclohexyl)_i,2,3,4-tetrahydronaphthalene

76.0 g (〇.26 mol) of 5,6-difluoro-3-(4-propylcyclohexyl)...in dihydronaphthalene in the presence of Pd/C (5% Pd) at room temperature and atmospheric pressure Hydrogenation for 19 hours in 〇〇ml THF 135213.doc 〇ς 200932735. The reaction solution was filtered and evaporated to dryness. The residue was used in the next reaction without further purification. 4.4 Preparation of 3,4-difluoro-6-(4-propylcyclohexyl)-5,6,7,8-tetrahydronaphthalen-2-ol

Initially, 77.0 g (about 0.26 mol) of crude 7,8-difluoro-2-(4-propylcyclohexyl)-1 1,2,3,4-tetrahydronaphthalene was introduced into 500 ml of THF at -70 ° 200.0 ml (0.32 mol) «-BuLi (15% solution in hexane) was added under C. After 3 hours at this temperature, 37.0 ml (0.33 mol) of acid-depleted trimethyl vinegar was added dropwise, the batch was warmed to 0 ° C, and 80 ml of dilute acetic acid (about 30%) was added. The mixture was warmed to 30 ° C' and 70 ml of a hydrogen peroxide solution (35%) was carefully added. c. After the addition was completed, the mixture was stirred at room temperature for 2 hours. Water was added and the batch was acidified using dilute hydrochloric acid. The solution was extracted several times with MTBE, and the combined organic phase was washed successively with water, a saturated sodium carbonate solution and an ammonium (II) sulfate solution. The solution was dried using sodium sulphate and evaporated to dryness. The crude product was purified by column chromatography (Si 2 , toluene). Further purification by recrystallization from n-heptane afforded 3, 'difluoro-6-(4-propylcyclohexyl)-5,6,7,8-tetrahydronaphthalene-2 as a colorless solid. age. • 4.5 Preparation of 6-(1-ethynylbutoxy)·7,8-difluoro-2-(4-propylcyclohexyl 1,2,3,4-tetrahydronaphthalene

135213.doc -96 - 200932735

Initially 7.0 g (22.7 mmol) of 3,4-difluoro-6-(4-propylcyclohexyl)-5,6,7,8-tetrahydronaphthalene-2- and 2.70 ml (24.0 mmol) l- Hex-3-ol and 6.60 g (25.2 mmol) of triphenylphosphine were introduced together into 90 ml of THF. 5.3 ml (46.8 mmol) DIAD in 10 ml of THF was added over 20 minutes under ice cooling. After 19 hours at room temperature, the mouth water was added and the mixture was extracted several times with MTBE. The combined organic phase was washed with water and a saturated sodium carbonate solution and the solution was dried using sodium sulfate. The residue remaining after removal of the solvent was purified by column chromatography ([jjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjj , 8-difluoro-2-(4-propylcyclohexyl)-1,2,3,4-tetrahydronaphthalene. 4.6 Preparation of 5,6-mono--3-propyl-8-(4-propylcyclohexyl)_7,8,9,1〇_tetrahydro-3Η-benzo[f]chromene

4·5 g(ll.6 mm〇l)6-(l-ethynylbutoxy)_7,8-difluoro-2-(4-propylcyclohexyl)-1,2,3,4-tetrahydronaphthalene 45 11111^,:^-diethyl phenylamine was heated for 2 hours under 135213.doc -97- 200932735. After cooling, the batch was added to a mixture of 2N hydrochloric acid and ice, and the mixture was extracted. The strip organic phase was washed with 2 -acid and water and the sodium sulfate dry solution was used. By column chromatography (10) 2'-n-heptane: benzene = 9:1), the residue remaining after removal of solvent was purified to give 5,6-difluoro_3_propyl winter (4) propyl as a yellow solid. Cyclohexyl)-7'8,9,1〇-tetrahydro_3H_benzo[f]chromene.

4.7 Preparation 5'6._敦_3_propyl_8_(4-propylcyclohexyl)_2 3,7,8,91〇_hexahydro-1H-benzo[f]chromene

5.0 g (about 11.4 mmol) of 5,6-difluoro-3-propyl-8 (4-propylcyclohexyl) in THF at atmospheric pressure and in the presence of Pd/C (5% Pd) _7,8,91〇_tetrahydro-3Η-stupid [f] olefin oxime. The reaction solution was filtered, and the filtrate was evaporated to dryness. The residue was purified by column chromatography (Si.sub.2, n-heptane: toluene = 9:1). Further purification by recrystallization from ethanol gives a 1:1 mixture of isomeric 5,6-difluoro-3-propyl-8-(4-propylcyclohexylbenzo[f]chromene (melting point) 89. 〇). For example, this material was resolved by preparative HPLC. 135213.doc -98- 200932735

Δε=-7.5 Δη=0.0879 C 89 Ν 113 I !H-NMR (500 MHz, CHC13): 6=4.01-3.90 (m, 1Η, 3-H), 2.84-2.77 (m, 1H), 2.69-2.22 (m, 5H), 2.07-1.93 (m, 2H), φ 1.86-1.66 (m, 5H), 1.62-1.43 (m, 4H), 1.41-1.26 (m, 4H), 1.24-1.11 (m, 4H ), 1.08-0.83 (m, 10H). 19F-NMR (376 MHz, CHC13): 8 = -146.4 (dd, IF, J = 21.1 Hz, J = 3.4 Hz), -165.9 (dd, IF, J = 21.1 Hz, J = 11.7 Hz). MS (El): m/e (%) = 390 (100, M+), 321 (78). Example 5: 8-Ethoxy-5,6-difluoro-3-(4-propylcyclohexyl)-2,3-dihydro-1H-benzo[f]chromene

5.1 Preparation of 7,8-difluoro-3-trimethyldecylnaphthalene-2-ol

50.0 g (0.26 mol) of 2,3-difluorophenyl acetamidine in 100 135213.doc •99·200932735 dioxane methane was slowly added to 715 g (0.53 mol) at -20 °C. Aluminum (ΠΙ) in a suspension of 300 ml of di-methane. After 30 minutes at this temperature, trimethyldecyl acetylene was weighed and the mixture was stirred for 3 minutes. The batch was added to ice water and acidified with hydrochloric acid. The organic phase was separated and the aqueous phase was extracted with ethyl acetate. The combined organic phases were washed sequentially with saturated sodium bicarbonate solution and saturated sodium hydride solution. The solution was dried using sodium sulfate and evaporated to dryness. Purification of the residue by column chromatography (Si.sub.2, n-heptane: ethyl acetate = 9:1) afforded 7,8-difluoro-3-trimethylsulfonyl-methyl as a brown oil. 2- hope. 5.2 Preparation of (3-ethoxy-5,6-difluoronaphthalen-2-yl)trimethyldecane

54.7 g (about 0.12 mol) of 7,8-difluoro-3-trimethyldecylalkylnaphthalen-2-ol and 19.5 ml (0.26 mol) of ethyl bromide and 34.5 g (〇.25 mol) at 80 °C Potassium carbonate was stirred together in 400 ml of ethyl methyl ketone for 19 hours. The batch was filtered and the residue was washed with ethyl decyl ketone. The filtrate was concentrated and the residue was dissolved in MTBE. The solution was washed with water and a saturated sodium carbonate solution and dried using sodium sulfate. The residue remaining after removal of the solvent was purified by column chromatography (Si.sub.2, toluene·ethyl acetate = 9:1) to afford (3-ethoxy- 5,6- Di-naphthalen-2-yl)trimethyl group is calcined. Preparation of 7-ethoxy-1,2-difluorocaline 5.3213.doc -100- 200932735

F F

44.0 g (about 81.6 mmol) of (3-ethoxy-5,6-difluoro-Cai-2-yl)trimethylnonane together with 26.3 g (0.17 mol) of cesium fluoride at 10 ° C Stir for 20 hours in 300 ml DMF. After cooling, the mixture was diluted with water and extracted multiple times with MTBE. The combined organic phase was washed with water and a saturated sodium chloride solution and the solution was dried using sodium sulfate. The brown oil remaining after removal of the solvent was purified by column chromatography (m.sub.2, toluene: ethyl acetate = 9:1) to afford 7-ethoxy-1,2- Flunan. 5.4 Preparation of 6-ethoxy-3,4-difluoronaphthalen-2-ol

1. /7-BuLi F, / 2. B(OMe)3 }=\ 3. H202, HOAcT H〇NX /=\ Initially 30.0 g (about 〇·1 m〇i) 7_ethoxy_12 _Difluoronaphthalene was introduced into 3〇〇^ THF and 13〇.〇mi(〇.21 m〇i)w_BULi (15% solution in hexane) was added at -75 C. After t hours at this temperature, 25. 〇 ml (0.22 mol) of dinonyl borate was added dropwise, and the batch was warmed to _1 Torr. Add 5 μμ dilute acetic acid (about 30%) 'and warm the mixture to 3 (Γ.: carefully add 4 〇 (4) hydrogen peroxide solution (35%), and drip the mixture vigorously for 8 hours. Add water And adding iron (π) ammonium sulfate to the batch. The solution is extracted multiple times with mtbe' and the combined organic phase is washed successively with water and a saturated gasified steel solution. The solution is dried using sodium sulfate and evaporated to dryness. Purification of the crude product by column chromatography (si〇2, toluene: ethyl acetate (tetra): hydrazine)

• 10U 135213.doc 200932735 6-ethoxy-3,4-difluoronaphthalen-2-ol in solid form 5.5 Preparation of 7-ethoxy-i,2-difluoro_3-[ 1-(4- Propylcyclohexyl)prop-2-ynyloxy]naphthalene

Initially 10.5 g (46.8 mmol) of 6-ethoxy-3,4-difluoronaphthalene-2- and 10.0 g (55.5 mmol) of l-(4-propylcyclohexyl)prop-2-yn-1-ol 15.0 g (57.2 mmol) of triphenylphosphine was introduced into 1 〇〇mi THF, and 11.5 ml (59.1 mmol) of DIAD was added over 20 minutes under ice cooling. After 18 hours at room temperature, water was added and the mixture was extracted multiple times with MTBE. The combined organic phases were washed with water and a saturated sodium carbonate solution, and the solution was dried using sodium sulfate. The residue remaining after removing the solvent was purified by column chromatography (Si 〇 2, n-heptane: MTBE = 2:1). Further purification by recrystallization from n-heptane to give 7-ethoxy-[,2-difluoro[1-(4-propylcyclohexyl)prop-2-ynyl as a pale yellow solid Oxy] naphthalene. 5.6 Preparation of 8-ethoxy-5,6-difluoro_3·(4-propylcyclohexyl)_3H benzo(7) chromene 135213.doc 102- 200932735

F F

7.75 g (about 18.6 mm 〇l) of 7-ethoxy dioxin _3_ ' Π-(4·propylcyclohexyl)propan-2-ynyloxy] naphthalene at 80 ml at 205 ° C Heated in NN_diethylbenzamine for 4.5 hours. The batch was diluted with MTBE and washed several times with hydrochloric acid. The organic phase was dried over sodium sulfate and evaporated to dryness. The residue was purified by column chromatography (Si 〇 2 </ </ RTI> </ RTI> </ RTI> <RTIgt; Further purification by recrystallization from n-heptane to give 8-ethoxy-5,6-difluoro-3-(4-propylcyclohexyl)·3Η-benzo[f] as a yellow solid. ] chromene. 5.7 Preparation of 8-ethoxy-5,6-di|^-3·(4-propylcyclohexyl)_2,3-dihydro-1H-benzo[f]chromene

F F

g(13.1 mm〇l)8-ethoxy_56_difluoro_3_(4-propylcyclohexyl)3H is abbreviated in THF at atmospheric pressure and in the presence of Pd/C (5°/〇Pd) And [f] dilute hydrogenation. The reaction solution was filtered, and the filtrate was evaporated to dryness. The residue was recrystallized from EtOAc (EtOAc: EtOAc: EtOAc: EtOAc: 3-Dihydro-1H-benzo[f]chromene (melting point 158. 〇.

Δε=-5.4 Δη=0.1550 C 158 Ν 159 I 1H_NMR (400 ΜΗζ, CHC13): δ=7.64 (dd, 1Η, J=9.2 Ηζ, J=1.6 Hz, 10-H), 7.24 (d, 1H, J =2.4 Hz, 7a-H), 7.12 (dd, 1H, J=9.2 Hz, J=2.4 Hz, 9-H), 4.14 (q, 2H, J=7.0 Hz, OCH2CH3), 3.84-3.79 (m, 1H, 3-H), 3.08-3.00 (m, 1H, 1-H), 2.97-2.87 (m, 1H, 1-H), 2.20-2.06 (m, 2H, H aliphatic), 1.94-1.79 ( m, 4H, H aliphatic), 1.71-1.60 (m, 1H, H aliphatic), 1.47 (t, 3H, J = 7.0 Hz, 〇CH2CH3), 1.38-1.11 (m, 7H, H aliphatic), 1.00-0.86 (m,5H, _H aliphatic) 19F-NMR (376 MHz, CHC13): 5=-152.5 (dd, IF, J = 17.8 Hz, J = 1.2 Hz), -160.5 (d, 1F, J=17.8 Hz). MS (El): m/e (%) = 388 (89, M+), 237 (100). 135213.doc -104-

Claims (1)

200932735 X. Patent application scope: 1. A compound of formula I: Wherein: m and η are each independently 0, 1, 2 or 3, wherein m+n $ 4 ; L1 and L2 each independently represent η, halogen, CN, CF3, chf2, CH2F or CH3; A1 and A2 Each independently represents (4) 1,4-phenylene, wherein =CH- may be substituted once or twice by =N_ and may be unsubstituted or independently of each other via -CN, -F, -Cl, _Br, - I, unsubstituted or It is a 7- or a gas-substituted or polysubstituted Ci-C6 alkyl group or a oxime-substituted or substituted with fluorine and/or chlorine. 6-yard oxy-monosubstituted to tetra-substituted, (b) 1,4-cyclohexylene, anthracene, 'cyclohexene-alkenyl or fluorene-cyclohexane-alkenyl' wherein _Cii2_ can be independently of each other - replacing 3 or 2 persons in a manner in which a hetero atom is not directly bonded and which may be unsubstituted or mono- or poly-substituted with -F and/or -C1, or (c) bicyclo 3 -I 丄, 3_-yl Bicyclo[2.2_2]octane-1,4-135213.doc 200932735 diyl or spiro[3.3]heptane-2,6-diyl; Z1 and Z2 each independently represent a single bond, -〇卩2〇- , -〇(^2-, _CH2CH2-, -CF2CF2-, _CF2CH2-, -CH2CF2-' -(CO)O- ' -O(CO)- ' -CH20- ' -〇CH2- ' -CF=CH- , -CH=CF-, _CF=CF-, _CH=CH_, a C=c_ or a combination of two of the groups, wherein the ruthenium atoms are not directly bonded; R1 and R2 represent hydrogen independently of each other, Unsubstituted, mono- or optionally substituted with -F, -C1 and/or -Br, alkyl, alkoxy, alkenyl having 1 to 15 or 2 to 15 C atoms, respectively Or alkynyl' wherein, in addition, one or more CH2 groups of the groups may each independently pass s_, -s〇2_, -CO-, -(co)o-, -O(CO)- or -〇(co)o-to the miscellaneous The sub-substitution is not directly linked, or represents _F, -Cl, -Br, -CN, -SCN, or -SF5; and ring B represents 135213.doc -2- 200932735 Where: ❹ A1 and A2 or Z1 and Z2, if „! or n is greater than 丨, may each have the same or different meanings, where: R1 and R2 do not indicate Η, and where: where R1=H and m=0 or In the case where R2 = H and η = 〇, then - Ο Β Β Β 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. F or both of the groups L1 and L2 represent F. 3. A compound according to claim 1 or 2, characterized in that the substituents L1 and L2 represent F ° 4. The compound of claim 1 is characterized in that The I compound is selected from the subtypes IA to IF: R1+A1-Z R1-|-A-Z 1C ID IE 135213.doc 200932735 R z, a, R, R, 2 -cf2o-, -0CF2-, -OCH2, -CH2〇-, _cf2CF2- ' -CH = CH-, -CF = CH-, -CH=CF- or _cf = CF-. 6. A compound as claimed in claim 1, characterized in that ^ and 八2 independently of each other represent a ring of the formula: The compound of the item 1 is characterized in that: 135213.doc 200932735 Rl and D2 are each independently an alkyl group, an alkoxy group or an alkenyl group having 1 to 7 or 2 to 7 carbon atoms, respectively. The groups are each unsubstituted or monosubstituted or polysubstituted by dentate, or represent fluorine or hydrogen. 8. The compound of claim 1, wherein all of the compounds are: zero, and each of R1 and R2, ❹ is independently an unbranched alkyl group or an alkane having 1 to 7 or 2 to 7 carbon atoms, respectively. Oxy or alkenyl. A1, A: 9. A compound of claim 1, characterized in that m+n=l, and Express independently of each other 10. Use of one or more compounds as claimed in any one of the preceding claims, wherein the use is in a liquid crystal medium. 11. A method comprising at least two compounds comprising at least one such as the medium of claim 15 which is characterized by a package such as a garment item -9 to a ninth item. Request the item LCD media. 135213.doc 200932735 13. A method for the preparation of a compound of formula I according to any one of claims 1 to 9, which comprises a method of using the A 1 ® - ΤΓ method, wherein The organic group is a compound of the formula: among them: Or a plurality of η, A2, and Z2 according to the formula I are as defined in claims 1 to 9, and R22 is as defined with respect to and additionally represents _〇Ts 〇Tf 〇Mes -b_)2, Na_ slave base) 2 or _b &lt; (〇c2. Stretching base _ 〇), etherified on the hydroxyl group to obtain a compound of the formula: Where &quot;...^^, ^ and ^ are as defined in the request item (1) or more than the definition of the formula I, mR22#'W is defined and can be additionally n meal · 〇μ", -B(0H)2, - B(0-alkyl) 2 or _B&lt;(〇_C2 烷基alkyl-〇), X represents -CH2CH2Br or -C=CH, and Y represents Η or Br; and in another method step 135213.doc 200932735 VII. Designated representative map: (1) The representative representative of the case is: (none) (2) The symbol of the symbol of the representative figure is simple: 8. If there is a chemical formula in this case, please reveal the best Chemical formula showing the characteristics of the invention: 135213.doc